Atypical Antipsychotics and use for Mood Disorders
On a personal note, I am bipolar II and am on Risperdal and it has made a world of difference with rage and intensity and obsessive thinking. That is how it has worked for one person. I am also on Alibify..a newer atypical antipsychotic with supposedly less side effects..ie less weight gain for instance. SINCE BEING PUT ON ABILIFY, I am not suffering from depression. My depression from Abilify has lifted. Paxil didn't touch it. Wellbutrin made me manic.
There is already a Patient Assistant's Program for Abilify http://www.needymeds.com which you can find by clicking on needymeds link.Click here if you wish to read about possible side effects of Zyprexa. Although there was recent article saying that research suggests that atypical antipsychotics may reduce risk of diabetes among bipolars, one wonders if one should be wary of Zyprexa.
Ann Pharmacother. 2003 Dec;37(12):1849-57. :
Relationship of atypical antipsychotics with development of diabetes mellitus.
Citrome LL, Jaffe AB.
New York University School of Medicine, New York, NY and Clinical Research and Evaluation Facility, Nathan S Kline Institute for Psychiatric Research, Orangeburg, NY, USA. citrome@nki.rfmh.org
OBJECTIVE: To review the pharmacoepidemiologic evidence for the link between exposure to atypical antipsychotics and the development of diabetes mellitus.DATA SOURCES: A MEDLINE search (1990-March 2003) was conducted.STUDY SELECTION AND DATA EXTRACTION: The search was limited to articles that described findings from analyses of large databases and used the words diabetes or hyperglycemia, and antipsychotic or clozapine or olanzapine or risperidone or quetiapine or ziprasidone or aripiprazole in the title or abstract. The odds ratio or relative risk, together with their corresponding confidence interval, was extracted.DATA SYNTHESIS: Results are conflicting, and this variability may be due to the different populations studied, different study designs, and the possibility of publication bias related to funding by the pharmaceutical industry. Nevertheless, an increased risk for diabetes mellitus appears to be present for patients receiving atypical antipsychotics. However, differential risk among the atypical antipsychotics is difficult to ascertain.CONCLUSIONS: Clinicians are urged to manage risk by regularly monitoring all patients receiving atypical antipsychotics for the emergence of diabetes mellitus. Future studies should carefully control for confounding variables such as age, diagnosis, change in weight, activity level, family history, and ethnicity. Pharmacotherapy. 2003 Nov;23(11):1411-5. :
Exploring the association between atypical neuroleptic agents and diabetes mellitus in older adults.
Etminan M, Streiner DL, Rochon PA.
Department of Clinical Epidemiology, Royal Victoria Hospital, McGill University, Montreal, Quebec, Canada. Mahyar.etminan@mail.mcgill.ca
STUDY OBJECTIVE: To explore the suggested association between atypical neuroleptic use and the development of diabetes mellitus, with a focus on older adults. DESIGN: Retrospective cohort study. SUBJECTS: Eleven thousand one hundred four older (> 65 yrs) residents of long-term care institutions in Ontario, Canada, who received either atypical neuroleptic agents, typical neuroleptic agents, benzodiazepines, or corticosteroids. MEASUREMENTS AND MAIN RESULTS: Each subject was followed for the development of a diabetic event, defined as newly prescribed antidiabetic drug therapy. Our Cox regression model was adjusted for age, sex, socioeconomic status, comorbidity, and concomitant use of beta-blockers, thiazide diuretics, and antiepileptic agents. The adjusted hazard ratio for the development of diabetes in patients receiving atypical neuroleptics compared with those receiving benzodiazepines (control group) was 0.89 (95% confidence interval [CI] 0.66-1.21). The adjusted hazard ratio for typical neuroleptic users compared with the benzodiazepine group was 1.27 (95% CI 0.91-1.77). As expected, patients receiving corticosteroid therapy were almost twice as likely to develop diabetes as those receiving benzodiazepines (adjusted hazard ratio 2.2, 95% CI 1.41-3.12). For patients receiving atypical neuroleptic agents, no statistically significant difference in the percentage of diabetic events was found among individual agents (2.1% olanzapine, 1% quetiapine, 2.1% risperidone). CONCLUSION: Drug therapy with atypical neuroleptic agents in older adults did not increase their risk of developing diabetes mellitus
AstraZeneca gets bipolar medication go-ahead
Mon 13 October, 2003 08:53 BST
LONDON (Reuters) - AstraZeneca, Europe's second-biggest drug-maker, says 14 European countries have given it the go-ahead to extend the use of Seroquel, a medication used to treat manic-depression.
Worldwide Seroquel sales grew 67 percent to $1.14 billion in 2002, AstraZeneca said in a statement on Monday. Manic depression, a serious mental illness also known as bipolar disorder, affects three to four percent of the adult population, it said. J Clin Psychopharmacol. 2003 Jun;23(3 Suppl 1):S9-14. :
Efficacy of atypical antipsychotics in mood disorders.
Yatham LN.
University of British Columbia, Vancouver, Canada. yatham@interchange.ubc.ca
Lithium and valproate are well recognized as mood-stabilizing medications. However, a significant number of patients with bipolar disorder do not respond to or cannot tolerate the side effects of these drugs. As a result, a search for safer and more effective mood stabilizers for the treatment of bipolar disorder is ongoing. Antipsychotic medications have long been used as adjunctive therapy in combination with mood-stabilizing medications. Although conventional neuroleptics (also known as typical antipsychotics) such as haloperidol or chlorpromazine are effective antimanic agents, they do not appear to have any efficacy in treating comorbid depressive symptoms. Furthermore, typical antipsychotics are associated with a number of well-known side effects, such as extrapyramidal symptoms and tardive dyskinesia. Mood-stabilizing effects have recently been reported for a number of newer "atypical" antipsychotics that have a broader spectrum of efficacy and better safety profiles than the typical antipsychotics. The results of several clinical trials suggest that atypical antipsychotics, including risperidone, olanzapine, ziprasidone, and quetiapine, are effective for the treatment of acute mania, and open-label studies suggest that atypical antipsychotics may have long-term mood-stabilizing effects. Psychopharmacology (Berl). 2003 Aug;168(4):410-6. Epub 2003 Apr 23.:
Comparison of the effects of antipsychotics on a delayed radial maze task in the rat.
Wolff MC, Leander JD.
Lilly Research Laboratories, Lilly Corporate Center, Eli Lilly and Company, Mail Code No. 0510, Indianapolis, IN 46285, USA. wolff_mary_c@lilly.com
RATIONALE: The cognitive impairments evident in many schizophrenics are related to the severity of their negative symptoms and ability to function in society. Drugs that alleviate cognitive impairments, in addition to other psychotic symptoms, may have an important influence on treatment outcome and the course of the illness. OBJECTIVES: A delayed non-match to sample task conducted in an eight-arm radial maze was used to determine the influence of four atypical antipsychotics (olanzapine, ziprasidone, risperidone, and clozapine), as well as a typical neuroleptic (haloperidol) on consolidation processes in healthy rats. METHOD: Well-trained rats were required to recall after a 7-h delay where they had received food pellets during an information phase (first four arm choices) in order to obtain the remaining food pellets during a retention phase (second four arm choices). RESULTS: The total number of errors that occurred during the retention session increased with increasing delay periods from 0 to 7 h. When administered orally immediately after the information phase, olanzapine (3 and 5 mg/kg) and risperidone (0.1 mg/kg) significantly reduced the number of errors made during the retention phase. Under the same conditions, clozapine, ziprasidone and haloperidol failed to affect the total number of retention phase errors. CONCLUSION: Some atypical antipsychotics, such as olanzapine and risperidone, improve consolidation processes and may alleviate the cognitive impairments associated with schizophrenia
Emerg Med J. 2003 Jul;20(4):339-46. :
Pharmacological management of agitation in emergency settings.
Yildiz A, Sachs GS, Turgay A.
Dokuz Eylul Medical School, Department of Psychiatry, Izmir, Turkey. Harvard Medical School, Massachussets General Hospital, Bipolar Program, Boston, USA. University of Toronto, Scarborough Hospital, Canada.
OBJECTIVE: To review, firstly, published studies comparing classic antipsychotics, benzodiazepines, and/or combination of both; and secondly, available data on the use of atypical antipsychotic medications in controlling agitation and aggressive behaviour seen in psychiatric patients in emergency. METHOD: In the first review, studies comparing antipsychotics, benzodiazepines, and combination of both; and in the second review, efficacy trials of atypical antipsychotics that include an active and/or inactive comparator for the treatment of acute agitation were identified and reviewed. Data from clinical trials meeting the inclusion criteria were summarised by recording improvement rates, definition of improvement, and timing of defined improvement for individual studies. RESULTS: In the first review, 11 trials were identified meeting the inclusion criteria, eight with a blind design. The total number of subjects was 701. These studies taken together suggest that combination treatment may be superior to the either agent alone with higher improvement rates and lower incidence of extrapyramidal side effects. In the review of atypical antipsychotic agents as acute antiagitation compounds, five studies were identified, three with a blind design. The total number of subjects was 711, of which 15% (104) was assigned to the placebo arm. This review found atypical antipsychotics to be as effective as the classic ones and more advantageous in many aspects. CONCLUSION: Atypical antipsychotics such as risperidone, ziprasidone, and olanzapine with or without benzodiazepines should be considered first in the treatment of acute agitation. If these agents are not available the combination of a classic antipsychotic and a benzodiazepine would be a reasonable alternative. An oral treatment should always be offered first for building up an alliance with the patient and suggesting an internal rather than external locus of control.
Int Clin Psychopharmacol. 2003 Jul;18(4):227-35. Related Articles, Links
Risperidone in acute and continuation treatment of mania.
Yatham LN, Binder C, Riccardelli R, Leblanc J, Connolly M, Kusumakar V; On behalf of the RIS-CAN 25 Study Group.
aDepartment of Psychiatry, University of British Columbia, Vancouver In a prospective study, we examined the efficacy of risperidone added-on to mood stabilizers in the acute and continuation treatment of mania over a 12-week period. Patients (n=108) with a DSM-IV diagnosis of bipolar disorder, manic or mixed episode requiring treatment with an antipsychotic were recruited. All subjects were on one or two mood stabilizers at the time of initiation of risperidone (range 0.5-4 mg). No other antipsychotic medication or ongoing benzodiazepine therapy was allowed. There was a significant decrease in mean Young Mania Rating Scale (YMRS) scores from baseline (27.5+/-7.5) to week 1 (-10.8, P < 0.0001), week 3 (-17.7, P<0.0001) and to week 12(-22.6, P < 0.0001). When response was defined as >/= 50% reduction in YMRS scores from baseline, 32%, 68% and 90% of patients met criteria at week 1, week 3 and week 12, respectively. Significant decreases in mean 21-item Hamilton Depression Rating Scale scores from baseline (12.2+/-7.7) to week 3 (-5.7, P < 0.0001) and week 12 (-5.7, P <0.0001) were also observed. No significant changes in extrapyramidal symptoms were noted between baseline and endpoint. The mean daily dose of risperidone was 2 mg with a median of 1.8 mg. These findings support the results of the two previous double-blind, randomized trials and indicate that the addition of risperidone to mood stabilizers is a safe and effective treatment for acute and continuation treatment of mania. Risperidone add-on does not induce depressive symptoms and, furthermore, risperi-done may have efficacy in treating comorbid depressive symptoms in bipolar patients.
Schizophr Res. 2003 Jul 1;62(1-2):77-88. :
Weight gain in patients with schizophrenia treated with risperidone, olanzapine, quetiapine or haloperidol: results of the EIRE study.
Bobes J, Rejas J, Garcia-Garcia M, Rico-Villademoros F, Garci;a-Portilla MP, Fernandez I, Hernandez G.
Department of Psychiatry, University of Oviedo, C/Julian Claveri;a, 6, 33006, Oviedo, Spain
OBJECTIVES: The aim of this cross-sectional study, the EIRE study, was to assess the frequency of several side effects with antipsychotics in the clinical setting. This paper addresses the adverse effect of weight gain. METHOD: Outpatients diagnosed of schizophrenia according to DSM-IV criteria and receiving a single antipsychotic (risperidone, olanzapine, quetiapine or haloperidol) for at least 4 weeks were consecutively recruited. Data were collected in a single visit, including data on demographic, clinical and treatment characteristics. Mean weight change was evaluated retrospectively by means of clinical charts and the weight at the time of the visit; in addition, the corresponding item of a modified version of the UKU, a Scandinavian side-effect rating scale, was used. Chi-squared test and logistic regression methods were used to analyze frequency of weight gain between treatments. RESULTS: Out of 669 recruited, 636 evaluable patients were assessed. The treatment with the highest number of patients with weight gain as an adverse reaction on the UKU scale was olanzapine (74.5%), followed by risperidone (53.4%) and haloperidol (40.0%). The proportion of patients with clinically relevant weight gain (>/=7% increase versus initial weight) was also higher with olanzapine (45.7%) than with risperidone (30.6%) and haloperidol (22.4%). Five patients (13.5%) treated with quetiapine had some degree of weight gain according to the UKU scale, although no patient showed a clinically relevant weight gain (>/=7%). Treatment with olanzapine and risperidone were identified as risk factors of weight gain versus haloperidol. The risk of weight gain was higher in women (OR: 4.4), overweight patients (OR: 3.0) and in patients with J Cardiovasc Pharmacol. 2003 Jun;41(6):934-7. :
Risperidone prolongs cardiac repolarization by blocking the rapid component of the delayed rectifier potassium current.
Drolet B, Yang T, Daleau P, Roden DM, Turgeon J.
Division of Clinical Pharmacology, Vanderbilt University School of Medicine, Nashville, Tennessee, U.S.A Cases of QT prolongation and sudden death have been reported with risperidone, a neuroleptic agent increasingly prescribed worldwide. Although hypokalemia was present in some of these events, we hypothesized that risperidone may have unsuspected electrophysiologic effects predisposing patients to proarrhythmia. In six isolated guinea pig hearts, risperidone elicited prolongation of cardiac repolarization: action potential duration increased from a baseline value of 128 ms +/- 5 to 147 ms +/- 5 (15%) with risperidone 1 microM during pacing at 250-ms cycle length, whereas the increase was only 10%, from 101 ms +/- 2 to 111 ms +/- 4, with pacing at a cycle length of 150 ms. In human ether-a-go-go (HERG)-transfected Chinese hamster ovary cells (n = 16), risperidone caused concentration-dependent block of the rapid component (I(Kr)) of the delayed rectifier potassium current with an IC(50) for tail block of 261 nM. Risperidone did not block I(Ks). Risperidone exerts cardiac electrophysiologic effects similar to those of Class III antiarrhythmic drugs. These effects are observed at clinically relevant concentrations. Because risperidone is metabolized primarily by CYP2D6, these actions likely enhance risk for risperidone-related QT prolongation and proarrhythmia in specific patient subsets (e.g., poor metabolizers and those taking interacting drugs).
J Clin Psychiatry. 2003 Jun;64(6):628-634. :
Risperidone in the Treatment of Schizotypal Personality Disorder.
Koenigsberg HW, Reynolds D, Goodman M, New AS, Mitropoulou V, Trestman RL, Silverman J, Siever LJ.
OBJECTIVE: Schizotypal personality disorder (SPD) has many phenomenological, genetic, physiologic, and neuroanatomical commonalities with schizophrenia. Patients with the disorder often suffer from marked social and occupational impairment, yet they have been difficult to treat with medications because of their unusual sensitivity to side effects. This study was designed to determine whether low-dose risperidone treatment is acceptable to SPD patients and can reduce characteristic schizotypal symptoms. In addition, if SPD patients respond to an antipsychotic medication, this will provide support for the notion of a commonality in treatment response between SPD and schizophrenia. METHOD: Twenty-five patients with DSM-IV-defined SPD were entered into a 9-week randomized, double-blind, placebo-controlled study of low-dose risperidone (starting dose of 0.25 mg/day, titrated upward to 2 mg/day) in the treatment of SPD. Patients were rated with the Positive and Negative Syndrome Scale (PANSS), the Schizotypal Personality Disorder Questionnaire, the Hamilton Rating Scale for Depression, and the Clinical Global Impressions scale. Data were collected from 1995 to 2001. RESULTS: The subjects had a low incidence of depression and of comorbid borderline personality disorder. Patients receiving active medication had significantly (p <.05) lower scores on the PANSS negative and general symptom scales by week 3 and on the PANSS positive symptom scale by week 7 compared with patients receiving placebo. Side effects were generally well tolerated, and there was no group difference in dropout rate for side effects. CONCLUSION: Low-dose risperidone appears to be effective in reducing symptom severity in SPD and is generally well tolerated.
J Clin Psychopharmacol. 2003 Jun;23(3 Suppl):S21-6. :
The implications of weight changes with antipsychotic treatment.
Sussman N. Patients receiving treatment with atypical antipsychotics commonly experience weight gain, which can cause considerable distress and can have deleterious effects on cardiovascular health. Because of the associated weight gain and potential direct effects on glucose metabolism, atypical antipsychotics have also been linked to the development of type II diabetes mellitus. Data on long-term treatment with these agents show that clozapine and olanzapine, followed by risperidone, were associated with the greatest degree of weight gain. A large body of data suggests that during long-term treatment, patients receiving the atypical antipsychotic quetiapine experience minimal weight gain. Data also suggest that quetiapine treatment does not increase the risk of developing type II diabetes. The use of atypical antipsychotics is increasing, as these agents are being prescribed for schizophrenia in lieu of conventional antipsychotics. Furthermore, these drugs have efficacy for treating other conditions such as bipolar disorder. Physicians prescribing atypical antipsychotics must be aware of the risk of weight gain and its associated comorbiditiess
J Clin Psychopharmacol. 2003 Jun;23(3 Suppl):S9-S14. :
Efficacy of atypical antipsychotics in mood disorders.
Yatham LN. Lithium and valproate are well recognized as mood-stabilizing medications. However, a significant number of patients with bipolar disorder do not respond to or cannot tolerate the side effects of these drugs. As a result, a search for safer and more effective mood stabilizers for the treatment of bipolar disorder is ongoing. Antipsychotic medications have long been used as adjunctive therapy in combination with mood-stabilizing medications. Although conventional neuroleptics (also known as typical antipsychotics) such as haloperidol or chlorpromazine are effective antimanic agents, they do not appear to have any efficacy in treating comorbid depressive symptoms. Furthermore, typical antipsychotics are associated with a number of well-known side effects, such as extrapyramidal symptoms and tardive dyskinesia. Mood-stabilizing effects have recently been reported for a number of newer "atypical" antipsychotics that have a broader spectrum of efficacy and better safety profiles than the typical antipsychotics. The results of several clinical trials suggest that atypical antipsychotics, including risperidone, olanzapine, ziprasidone, and quetiapine, are effective for the treatment of acute mania, and open-label studies suggest that atypical antipsychotics may have long-term mood-stabilizing effects.J Clin Psychopharmacol. 2003 Jun;23(3 Suppl):S2-8. :
Unmet clinical needs in bipolar disorder.
Sachs GS.
Bipolar disorder is a complex, chronic condition associated with considerable morbidity and mortality, including a high rate of suicide. Currently available treatment options for bipolar disorder fail to adequately address many of the important needs of bipolar patients. Long-term maintenance therapy with lithium has been shown to prevent further episodes of mania and depression and to decrease the likelihood of suicide. However, many patients stop lithium treatment after only a few weeks, because of either untoward side effects or other factors, such as the belief that they no longer require medication. Even when lithium is taken regularly and at adequate doses, many patients continue to exhibit severe functional disability and also fail to achieve remission. Bipolar depression is also poorly understood and difficult to treat. A number of adjunctive medications are used in combination with lithium, but residual symptoms and recurring episodes of mania and depression remain common. Recently, atypical antipsychotics, such as olanzapine, risperidone, and quetiapine, have been evaluated for the treatment of bipolar disorder. Although considerable research is still needed, preliminary findings suggest that some of these agents may act as mood stabilizers, improving the acute symptoms of mania without inducing depression or rapid cycling. The role of atypical antipsychotics in maintenance therapy for bipolar disorder is currently being evaluated in a number of large clinical trials.
: Pharmacotherapy. 2003 Jun;23(6):735-44. :
Risperidone-associated diabetes mellitus: a pharmacovigilance study.
Koller EA, Cross JT, Doraiswamy PM, Schneider BS.
Division of Metabolic and Endocrine Drug Products, Center for Drug Evaluation and Research, Food and Drug Administration, Rockville, Maryland, USA.
STUDY OBJECTIVE: To explore the clinical characteristics of hyperglycemia in patients treated with risperidone. DESIGN: Pharmacovigilance survey of spontaneously reported adverse events in risperidone-treated patients, with reports of haloperidol-associated hyperglycemia used as a control. SETTING: Government-affiliated drug evaluation center. INTERVENTION: The Food and Drug Administration MedWatch surveillance program was queried (risperidone, 1993-February 2002; haloperidol, late 1970s-February 2002) and results pooled with published cases. MEASUREMENTS AND MAIN RESULTS: We identified 131 reports of risperidone-associated hyperglycemia in addition to seven reports of patients with hyperglycemia who received combined risperidone-haloperidol therapy and six reports of acidosis that occurred in the absence of hyperglycemia. We found 13 reports of haloperidol-associated hyperglycemia and 11 reports of acidosis without hyperglycemia. Of the reports of risperidone-associated hyperglycemia (monotherapy), 78 patients had newly diagnosed hyperglycemia, 46 had exacerbated preexisting diabetes, and 7 could not be classified. Mean +/- SD age was 39.8 +/- 17.4 years (range 8-96 yrs). Patients with new-onset diabetes (mean +/- SD age 34.8 +/- 15.7 yrs) were younger than those with preexisting diabetes (mean +/- SD age 48.8 +/- 17.5 yrs). The overall male:female ratio was 1.5. In most patients, hyperglycemia appeared within 3 months of the start of risperidone therapy. Severity of disease ranged from mild glucose intolerance to diabetic ketoacidosis or hyperosmolar coma. Twenty-six patients with acidosis or ketosis were reported. Four patients died. CONCLUSION: Atypical antipsychotic treatment may unmask or precipitate hyperglycemia. Although such cases attributed to clozapine or olanzapine are more numerous than those associated with risperidone, the number for risperidone-associated hyperglycemia is relatively higher than that observed with the conventional neuroleptic haloperidol.
Actas Esp Psiquiatr. 2003 May;31(3):149-155. :
[Up-date in the treatment of rapid cycling and other refractory bipolar disorders]
[Article in Spanish]
Fernandez I, De Frutos M, Lujan E, Ortiz Del Romero J.
Introduction: Up-date in the treatment of rapid cycling and other resistant bipolar disorders. Methods: A Medline research of the literature was performed in several databases as Pub-Med, Cochrane and Embasse, from 1998 to December 2001. We have also reviewed bibliography supplied by different laboratories and several monographies. Results: 30 articles were selected: 11 reviews, 17 openlabeled studies and 2 articles on general recommendations. From the 17 open-labaled studies, 10 were on topiramate (25 to 400 mg/day) as a coadjuvant of another stabilizer. Improvement ranged from 40 to 70%; 4 adding gabapentin to the previous treatment, at the dosage of 60 to 5,600 mg/day, 27 and 92% showed improvement; 1 with mexiletine (200 to 1,200 mg/day) in which 46% were full responders, 15% partial responders and 38 % had no response, 100% response in manic or mixed and 38 % in depressed patients; and 2 with lamotrigine (50 to 500 mg/day) in which 52 to 80 % showed improvement. With risperidone at the dosage of 2-3 mg/day as coadjuvant, improvement was seen in 62 %. Olanzapine had direct short-term antimanic effects, with 49 % improvement in single drug therapy and 57 % as coadjuvant. Conclusions: More double-blind studies are necessary to assess efficacy in monotherapy or as coadjuvants, in short-term or even in monotherapy, and to compare the different treatments with each other as well as with the conventional treatment. The authors agree in pointing out the efficacy of gabapentin and topiramate associated to another stabilizer, and also of lamotrigine in depressed phases. Actas Esp Psiquiatr 2003;31(3):149-155
J Clin Psychopharmacol. 2003 Apr;23(2):193-6. :
Low-dose risperidone as adjunctive therapy for irritable aggression in posttraumatic stress disorder.
Monnelly EP, Ciraulo DA, Knapp C, Keane T.
Increased aggressive behavior can occur in association with posttraumatic stress disorder (PTSD). This study tested the hypothesis that low-dose risperidone reduces aggression and other PTSD-related symptoms in combat veterans. Subjects were male combat veterans with PTSD who scored 20 or higher on cluster D (hyperarousal) of the Patient Checklist for PTSD-Military Version (PCL-M). Subjects were randomly assigned to either risperidone or placebo treatment groups. Drugs were administered over a 6-week treatment period in a double-blind manner. Subjects received either risperidone (0.5 mg/day; n = 7) or matched placebo (n = 8) tablets during the first 2 weeks of the treatment period. The dose of risperidone could then be increased up to 2.0 mg/day on the basis of response. Prerandomization psychotropic regimens were continued. Subjects were evaluated with the PCL-M and the Overt Aggression Scale-Modified for Outpatients (OAS-M). In comparison with placebo treatment, reductions in scores between baseline and the last week of treatment were significantly greater for OAS-M irritability and PCL-M cluster B (intrusive thoughts) subscales and on the PCL-M total scale. These results suggest that low-dose risperidone administration reduces irritability and intrusive thoughts in combat-related PTSD.
large writeup on bipolar review with atypical antipychoticsLancet 2003 May 10;361(9369):1581-9 :
New generation antipsychotics versus low-potency conventional antipsychotics: a systematic review and meta-analysis.
Leucht S, Wahlbeck K, Hamann J, Kissling W.
Klinik und Poliklinik fur Psychiatrie und Psychotherapie der Technischen Universitat Munchen, Klinikum rechts der Isar, Munchen, Germany. stefan.leucht@lrz.tum.de BACKGROUND: The clearest advantage of new generation, atypical antipsychotics is a reduced risk of extrapyramidal side-effects (EPS), compared with conventional compounds. These findings might have been biased by the use of the high-potency antipsychotic haloperidol as a comparator in most of the trials. We aimed to establish whether the new drugs induce fewer EPS than low-potency conventional antipsychotics. METHODS: We did a meta-analysis of all randomised controlled trials in which new generation antipsychotics had been compared with low-potency (equivalent or less potent than chlorpromazine) conventional drugs. We included studies that met quality criteria A or B in the Cochrane Collaboration Handbook, and assessed quality with the Jadad scale. The primary outcome of interest was the number of patients who had at least one EPS. We used risk differences and 95% CIs as measures of effect size. FINDINGS: We identified 31 studies with a total of 2320 participants. Of the new generation drugs, only clozapine was associated with significantly fewer EPS (RD=-0.15, 95% CI -0.26 to -0.4, p=0.008) and higher efficacy than low-potency conventional drugs. Reduced frequency of EPS seen with olanzapine was of borderline significance (-0.15, -0.31 to -0.01, p=0.07). Only one inconclusive trial of amisulpride, quetiapine, and risperidone and no investigations of ziprasidone and sertindole were identified, but some evidence indicates that zotepine and remoxipride do not lead to fewer EPS than low-potency antipsychotics. Mean doses less than 600 mg/day of chlorpromazine or its equivalent had no higher risk of EPS than new generation drugs. As a group, new generation drugs were moderately more efficacious than low-potency antipsychotics, largely irrespective of the comparator doses used. INTERPRETATION: Optimum doses of low-potency conventional antipsychotics might not induce more EPS than new generation drugs. Potential advantages in efficacy of the new generation drugs should be a factor in clinical treatment decisions to use these rather than conventional drugs.
Diabetes Care 2003 May;26(5):1597-605 :
Patients on Atypical Antipsychotic Drugs: Another high-risk group for type 2 diabetes.
Lean ME, Pajonk FG.
Department of Human Nutrition, University of Glasgow, Glasgow, U.K. Department of Psychiatry and Psychotherapy, the Saarland University Hospital, Homburg, Germany.
Patients with schizophrenia are more likely than the general population to develop diabetes, which contributes to a high risk of cardiovascular complications; individuals with schizophrenia are two to three times more likely to die from cardiovascular disease than the general population. The risk of diabetes, and hence cardiovascular disease, is particularly increased by some of the new atypical antipsychotic drugs. Individuals taking an atypical antipsychotic drug, particularly younger patients under 40 years of age (odds ratio 1.63, 95% CI 1.23-2.16), represent an underrecognized group at high risk of type 2 diabetes. The mechanisms responsible for antipsychotic-induced diabetes remain unclear. Hypotheses include these drugs' potential to cause weight gain, possibly through antagonism at the H(1), 5-HT(2A), or 5-HT(2C) receptors. Other mechanisms independent of weight gain lead to elevation of serum leptin and insulin resistance. Patients with psychoses have difficulties with diet and lifestyle interventions for diabetes and weight management. If hyperglycemia develops, withdrawal from antipsychotic medication will often be inappropriate, and a change to an atypical antipsychotic drug with lower diabetogenic potential should be considered, especially in younger patients. Management of psychoses should routinely include body weight and blood glucose monitoring and steps to promote exercise and minimize weight gain. Careful collaboration between the psychiatric and diabetology teams is essential to minimize the risk of diabetes in patients taking atypical antipsychotic medication and for effective management when it develops. This collaboration will also help minimize the already high risk of cardiovascular disease in individuals with schizophreniaHyperprolactinemia-- elevated serum prolactin- excellent writeup " Drugs that may cause the condition include the following:
Dopamine receptor antagonists (eg, phenothiazines, butyrophenones, thioxanthenes, risperidone, metoclopramide, sulpiride, pimozide)
Dopamine-depleting agents (eg, methyldopa, reserpine)
Others (eg, isoniazid, danazol, tricyclic antidepressants, monoamine antihypertensives, verapamil, estrogens, antiandrogens, cyproheptadine, opiates, H2-blockers [cimetidine], cocaine)
" "The dopamine agonist, bromocriptine mesylate, is the initial drug of choice. It lowers the prolactin level in 70-100% of patients. Agents other than bromocriptine have been used (eg, cabergoline, quinagolide). Cabergoline and pergolide are available in the United States. Cabergoline, in particular, probably is more effective and causes fewer adverse effects than bromocriptine. However, it is much more expensive. Cabergoline often is used in patients who cannot tolerate the adverse effects of bromocriptine or in those who do not respond to bromocriptine. Pergolide has not been approved by the US Food and Drug Administration (FDA) for use in patients with this condition.
"Psychoneuroendocrinology 2003 Apr;28 Suppl 2:69-82 :
Hyperprolactinemia in response to antipsychotic drugs: characterization across comparative clinical trials.
Kinon BJ, Gilmore JA, Liu H, Halbreich UM.
Lilly Research Laboratories, Eli Lilly and Company, Lilly Corporate Center, Indianapolis, 46285, Indiana, USA
BACKGROUND: Atypical antipsychotic drugs for the treatment of schizophrenia provide effective treatment of psychotic symptoms with a safety profile superior to conventional antipsychotic medications. Neuroendocrine abnormalities in patients with schizophrenia, such as chronic hyperprolactinemia, may now potentially be minimized by the use of newer prolactin-sparing antipsychotic drugs. A discrimination of prolactin-sparing versus prolactin-elevating antipsychotic drugs may provide the clinician with treatment choices in order to avoid or mitigate hyperprolactinemia-associated morbidity.METHODS: Results from five clinical trials were used to characterize factors that may influence antipsychotic drug effects on levels of serum prolactin. Factors investigated included drug treatment, gender, time course, potential for reduction or reversibility, and age.RESULTS: Factors that influenced the risk of hyperprolactinemia included gender, with females appearing to be more sensitive than males, and drug treatment, with risperidone and conventional antipsychotic agents increasing prolactin more than olanzapine. Patients of all ages demonstrated sensitivity to increased prolactin. Furthermore, patients with hyperprolactinemia sustained the effect over time. Hyperprolactinemia reversed when patients were switched to a prolactin-sparing antipsychotic medication.CONCLUSION: Effects of antipsychotic medications on serum prolactin are multi-factorial. Evidence for sexual, reproductive, and general medical consequences of antipsychotic-induced hyperprolactinemia is developing, and identifying antipsychotic drugs with a favorable prolactin profile would be important in mitigating these consequences. Most notably for women, atypical or novel antipsychotic drugs with a prolactin-sparing profile may offer effective clinical treatment with preservation of physiological hormonal function.
Int Clin Psychopharmacol 2003 May;18(3):143-5 :
The efficacy of olanzapine monotherapy for acute hypomania or mania in an outpatient setting.
Dennehy EB, Doyle K, Suppes T.
Randomized controlled trials have demonstrated the efficacy of olanzapine for treating acute mania or depression symptoms in patients with bipolar disorder. We aimed to evaluate the effectiveness of this medication in more usual care outpatient settings. A consecutive series of 15 patients entered an open, uncontrolled 8-week trial of olanzapine monotherapy. Inclusion criteria included significant hypomanic or manic symptoms greater than or equal to 15 on the Young Mania Rating Scale and no psychotic symptoms. The majority of patients experienced significant decreases in mania ratings and more limited improvement on depression ratings. Most patients reported adverse events consistent with other studies, but few discontinued due to these complaints. This case series highlights the individual variation in response to a proven medication. Furthermore, it highlights that those medications effective at one end of the mood spectrum may not be equally or simultaneously effective with other symptoms, emphasizing the complexity of treating bipolar illness.Seroquel (Quetiapine) 25 mg 100 $74.43
Seroquel (Quetiapine) 100 mg 100 $146.88
Seroquel (Quetiapine) 200 mg 100 $278.11 Psychopharmacology (Berl) 2003 Apr;166(4):315-32
:
Atypical antipsychotics and mood stabilization in bipolar disorder.
Brambilla P, Barale F, Soares JC.
Department of Psychiatry, Division of Mood and Anxiety Disorders, University
of Texas Health Science Center at San Antonio, 7703 Floyd Curl Drive, TX
78229, San Antonio, USA. The available literature on the use of atypical antipsychotics for the treatment
of bipolar disorder was reviewed. All uncontrolled and controlled reports were
identified through a comprehensive Medline search. Based on the available
evidence, olanzapine was found to be the most appropriate atypical
antipsychotic agent utilized for the treatment of manic bipolar patients,
although there is also preliminary data suggesting the efficacy of risperidone
and clozapine. The preliminary data evaluating the efficacy of quetiapine and
ziprasidone in bipolar disorder are still very limited. Double-blind controlled
studies with atypical antipsychotics in the long-term treatment of bipolar
disorder are still largely not available, but will be critical to determine the
effectiveness of these agents in the maintenance treatment of bipolar disorder.
There are recent uncontrolled suggestions that olanzapine may have beneficial
effects in depressed bipolar patients, which deserve further investigation in
controlled studies. In conclusion, atypical antipsychotics, due to lower potential
for neurotoxicity and preliminary evidence suggesting better efficacy than
typical antipsychotics, are increasingly having a more prominent role in the
pharmacological management of bipolar patients. Nonetheless, until there is
systematic data from long-term controlled follow-up studies on the comparative
efficacy of these agents with mood stabilizers, atypical antipsychotics should
be cautiously utilized, and preferably in combination with a mood stabilizer for
the maintenance phase of treatment.Bipolar Disord 2003 Feb;5(1):72-75
:
Ziprasidone-associated mania: a case series and review of the
mechanism.
Baldassano C, Ballas C, Datto S, Kim D, Littman L, O'Reardon J, Rynn
M. Atypical antipsychotics are now commonly used in the treatment of bipolar
disorder, as they have been shown to have effects on mania as well as psychosis.
Shortly after the introduction of atypical antipsychotics, several cases of
associated hypomania and mania were reported. Ziprasidone is an atypical
antipsychotic recently approved by the Food and Drug Administration for the
treatment of psychosis. Although ziprasidone has also been shown to be
effective in treating mania, it may be associated with the induction of mania or
hypomania. We report four cases of mania associated with initiation of
ziprasidone, which, to our knowledge, are the first reported for this drug in
bipolar patients. As ziprasidone has substantial serotonergic and noradrenergic
action, we hypothesize, it may more likely induce mania than other atypical
antipsychotics. We advocate future studies to evaluate ziprasidone's efficacy
in treating bipolar disorder and caution clinicians that induction of mania or
hypomania may be possible with this agent.Pharmacopsychiatry 2002 Nov;35(6):205-19 :Baptista T, Kin NM, Beaulieu S, de Baptista EA.
Los Andes University School of Medicine, Department of Physiology, Merida, Venezuela. baptri@douglas.mcgill.ca
Excessive body weight gain (BWG) is a common side effect of some typical and atypical antipsychotic drugs (APs). Convergent evidence suggests a hierarchy in the magnitude of BWG that may be induced by diverse agents, being very high for clozapine and olanzapine; high for quetiapine, zotepin, chlorpromazine, and thioridazine; moderate for risperidone and sertindole; and low for ziprazidone, amisulpiride, haloperidol, fluphenazine, pimozide, and molindone. BWG may be related to increased appetite that is due to drug interaction with the brain monoaminergic and cholinergic systems and to the metabolic/endocrine effects of hyperprolactinemia. Subjects with schizophrenia and bipolar disorders manifested a significantly high prevalence of diabetes, even before the introduction of atypical APs. However, clozapine and olanzapine appear to display a high propensity to induce glucose dysregulation and dyslipidemia. Sudden BWG, insulin resistance, increased appetite, and related endocrine changes also may be involved in the development of glucose intolerance and dyslipidemia in predisposed individuals. Patients should be informed of these side effects in order to prevent excessive BWG, and their blood glucose and lipids should be monitored before treatment and then at regular intervals. Nutritional advice must be given and regular physical exercise recommended. An appropriate selection of APs ought to be based on drug efficacy for specific patients and assessment of relevant risk factors such as propensity to gain weight; family or personal history of diabetes or hyperlipidemia; and elevated fasting serum glucose, lipid, or insulin levels. At present, there is no standardized pharmacological treatment for AP-induced BWG. Some studies have assessed the effects of agents such as amantadine, orlistat, metformin, nizatidine, and topiramate on AP-induced BWG. Further studies will provide tools to identify patients at high risk for obesity and metabolic abnormalities during AP administration. Excessive body weight gain (BWG), glucose intolerance, and dyslipidemia during treatment with antipsychotic drugs (APs) were reported in the late 1950s [14,101]. However, after 1990, interest in these problems increased noticeably, mainly because of the high propensity of some new atypical APs to induce these side effects (Fig.1). The APs are currently used in diverse mental disorders. Hence, excessive BWG and metabolic dysfunction are not exclusive of subjects with schizophrenia. In the case of bipolar disorders, AP-induced BWG may be additive to that induced by mood stabilizers [14,48,101]. The clinical features [2,14,24,133,139,140] and mechanisms [14,34,68,87,93,101,130] of BWG and metabolic dysfunction have been previously reviewed. In this article, we focus on a unified theory to explain these side effects, based on the interaction of APs with brain neurotransmitters involved in appetite regulation. This review comprises the following sections: 1) the clinical features of AP-induced BWG; 2) the effects of APs on carbohydrate and lipid metabolism in humans and experimental animals; 3) mechanisms involved in BWG, glucose, and lipid dysregulation; 4) strategies for prevention and treatment of these side effects; and 5) research perspectives in the field. The following sources were consulted: MEDLINE, Cochrane database system, and PsychINFO. Numerous articles referred to in leading articles also were consulted. The literature on this subject has increased so rapidly that it was impossible to include all the data recently published. For the first two sections, references that illustrate current controversies in the field were selected.
J Affect Disord 2003 Jan;73(1-2):147-53
:
Placebo-controlled trials do not find association of olanzapine with
exacerbation of bipolar mania.
Baker RW, Milton DR, Stauffer VL, Gelenberg A, Tohen M.
Lilly Research Laboratories, Eli Lilly and Company, Lilly Corporate Center,
Drop Code 4133, 46285, Indianapolis, IN, USA BACKGROUND: Published case reports describe apparent induction or
exacerbation of manic-like symptoms during treatment with the atypical
antipsychotics olanzapine and risperidone. To date, such reports are from
uncontrolled clinical experience and therefore cannot clarify whether the
atypical antipsychotics caused such manic-like states or simply failed to
prevent them. Presumably, bipolar patients would be at increased risk for this
putative adverse event. Therefore, we evaluated the potential of olanzapine to
exacerbate symptoms of mania compared to placebo during treatment of bipolar
mania. METHODS: Two inpatient, double-blind, randomized trials investigating
the efficacy of olanzapine 5-20 mg daily versus placebo for the treatment of
acute mania were combined. Two hundred and fifty-four subjects participated
(placebo n=129; olanzapine n=125) in the two studies. Severity of mania was
quantified with the 11-item Young-Mania Rating Scale (Y-MRS). In a post-hoc
analysis, after double-blind therapy up to 3 weeks, categorical comparison of
olanzapine and placebo groups was made for any worsening and worsening by 10
or 20% from baseline Y-MRS scores (LOCF). RESULTS: The percentage of
subjects with exacerbation at endpoint were: any worsening, placebo 37.7%,
olanzapine 21.8% (P=0.005); >/=10% worsening, placebo 24.6%, olanzapine
14.5% (P=0.039); >/=20% worsening, placebo 15.6%, olanzapine 8.1% (P=0.064).
CONCLUSION: Mania rating scores worsened for some patients during
olanzapine therapy. However, this was significantly less common with olanzapine
than with placebo. These controlled data suggest that clinical case reports of
occurrence of 'mania' during treatment with olanzapine, and possibly those with
other atypical antipsychotics, reflect exacerbation in the natural history of
bipolar illness, rather than an adverse pharmacological effect.
LIMITATIONS: Post-hoc analysis of pooled data from two different studies. Actas Esp Psiquiatr 2003 Jan-Feb;31(1):40-7
:
[New treatment for bipolar disorder in children and adolescents:
learning from adult studies]
[Article in Spanish]
Soutullo C, Barroilhet S, Landecho I, Ortuno F. Background. Up to 45% of bipolar patients fail to respond adequately to or do
not tolerate treatment with standard antimanics (lithium, valproate,
carbamazepine, or olanzapine). Several new potential normothymic and
antimanic treatments are under study. However, there is less literature
available on new treatments for bipolar disorder in children and adolescents,
but many youths with manic symptoms are treated with mood stabilizers. Our
goal was to review the current literature on alternatives to lithium, valproate
and carbamazepine in the treatment of bipolar disorder in children, adolescents
and adults, focusing on the potential uses of these drugs in youth. Methods. In a
comprehensive computerized and manual literature search in Medline, we
identified articles, abstracts and book chapters describing new treatments for
bipolar disorder in children, adolescent, and adults. We also manually searched
the abstracts in recent APA, AACAP and ECNP Annual Meetings. Results. There
are very few studies on the treatment of youths with bipolar disorder. The
strongest evidence of antimanic action in this age group is on lithium, valproate,
and recently on olanzapine, and adjunctive risperidone. Evidence on new
antiepileptics and other novel treatments is very limited or none. Conclusion.
More controlled studies on the treatment of children and adolescents with
bipolarity are needed. Lithium, valproate, olanzapine and risperidone are
probably the drugs with more evidence as antimanic efficacy in children and
adolescents, but potential risks and benefits of treatment versus no treatment
must be discussed with parents. Actas Esp Psiquiatr 2003;31(1):40-7Atypical antipsychotics for managing Mood disorders Br J Psychiatry 2003 Feb;182:141-7
:
Mood stabilisers plus risperidone or placebo in the treatment of
acute mania. International, double-blind, randomised controlled
trial.
Yatham LN, Grossman F, Augustyns I, Vieta E, Ravindran A.
University of British Columbia, Vancouver, Canada. yatham@interchange.ubc.ca BACKGROUND: Few double-blind trials have examined the efficacy of a
combination of a mood stabiliser and an atypical antipsychotic in acute mania.
AIMS: To determine the efficacy of risperidone in combination with a mood
stabiliser in acute mania. METHOD: Patients taking a mood stabiliser were
randomised to 3 weeks' treatment with risperidone (n=75) or placebo (n=76).
RESULTS: Young Mania Rating Scale (YMRS) scores improved rapidly with
significantly greater reductions at week 1 in the risperidone group compared
with the placebo group. At end-point YMRS scores decreased by 14.5 and 10.3
points in the risperidone and placebo groups, respectively. Significant
improvements v. placebo (P<0.05) were noted in the risperidone group on several
other clinically meaningful measures. Additionally, a post hoc analysis excluding
carbamazepine-treated patients (plasma concentrations of risperidone active
moiety were 40% lower in this group) revealed significantly greater reductions
(P=0.047) in YMRS scores in the risperidone group than in the placebo group.
Incidence of adverse events was similar in both groups. CONCLUSIONS:
Risperidone is superior to placebo when used in combination with lithium or
divalproex in acute mania.: J Affect Disord 2003 Jan;73(1-2):147-53 :
Placebo-controlled trials do not find association of olanzapine with exacerbation of bipolar mania.
Baker RW, Milton DR, Stauffer VL, Gelenberg A, Tohen M.
Lilly Research Laboratories, Eli Lilly and Company, Lilly Corporate Center, Drop Code 4133, 46285, Indianapolis, IN, USA
BACKGROUND: Published case reports describe apparent induction or exacerbation of manic-like symptoms during treatment with the atypical antipsychotics olanzapine and risperidone. To date, such reports are from uncontrolled clinical experience and therefore cannot clarify whether the atypical antipsychotics caused such manic-like states or simply failed to prevent them. Presumably, bipolar patients would be at increased risk for this putative adverse event. Therefore, we evaluated the potential of olanzapine to exacerbate symptoms of mania compared to placebo during treatment of bipolar mania. METHODS: Two inpatient, double-blind, randomized trials investigating the efficacy of olanzapine 5-20 mg daily versus placebo for the treatment of acute mania were combined. Two hundred and fifty-four subjects participated (placebo n=129; olanzapine n=125) in the two studies. Severity of mania was quantified with the 11-item Young-Mania Rating Scale (Y-MRS). In a post-hoc analysis, after double-blind therapy up to 3 weeks, categorical comparison of olanzapine and placebo groups was made for any worsening and worsening by 10 or 20% from baseline Y-MRS scores (LOCF). RESULTS: The percentage of subjects with exacerbation at endpoint were: any worsening, placebo 37.7%, olanzapine 21.8% (P=0.005); >/=10% worsening, placebo 24.6%, olanzapine 14.5% (P=0.039); >/=20% worsening, placebo 15.6%, olanzapine 8.1% (P=0.064). CONCLUSION: Mania rating scores worsened for some patients during olanzapine therapy. However, this was significantly less common with olanzapine than with placebo. These controlled data suggest that clinical case reports of occurrence of 'mania' during treatment with olanzapine, and possibly those with other atypical antipsychotics, reflect exacerbation in the natural history of bipolar illness, rather than an adverse pharmacological effect. LIMITATIONS: Post-hoc analysis of pooled data from two different studies.: Psychoneuroendocrinology 2003 Jan;28 Suppl 1:83-96 Related Articles, Links
A review of the effect of atypical antipsychotics on weight.
Nasrallah H.
Department of Psychiatry, University of Cincinnati Medical Center, 231 Albert Sabin Way, P.O. Box 670559, 45267-0559, Cincinnati, OH, USA
Controlled research trials have shown that atypical antipsychotics have important advantages over standard antipsychotics, including a broader spectrum of efficacy and improved tolerability profile, particularly with regard to neurological adverse events such as extrapyramidal symptoms (EPS). Some atypical antipsychotics, however, tend to cause significant weight gain, which may lead to poor compliance and other adverse health effects. The mechanisms involved in antipsychotic drug-related weight gain are as yet uncertain, although serotoninergic, histaminic, and adrenergic affinities have been implicated along with other metabolic mechanisms. The atypical antipsychotics vary in their propensity to cause weight change with long-term treatment. Follow-up studies show that the largest weight gains are associated with clozapine and olanzapine, and the smallest with quetiapine and ziprasidone. Risperidone is associated with modest weight changes that are not dose related. Given the equivalent efficacy of atypical antipsychotics, weight-gain profile is a legitimate factor to consider when constructing an algorithm for treatment due to the serious medical consequences of obesity J Clin Psychiatry 2002 Dec;63(12):1135-9
:
The risk of diabetes during olanzapine use compared with
risperidone use: a retrospective database analysis.
Caro JJ, Ward A, Levinton C, Robinson K.
Caro Research Institute, Concord, Mass, USA. jcaro@caroresearch.com BACKGROUND: The relative risk of diabetes among patients undergoing
risperidone treatment was compared with that of patients receiving olanzapine.
METHOD: A cohort was formed of 33,946 patients with at least 1 prescription
for either olanzapine (N = 19,153) or risperidone (N = 14,793) between
January 1, 1997, and December 31, 1999, recorded in the Regie de l'Assurance
Maladie du Quebec database. Patients were excluded if clozapine was dispensed
to them during the study period or if they were diagnosed with diabetes before
beginning antipsychotic therapy. New diabetes diagnoses made after the first
antipsychotic prescription during the period were tabulated until December 31,
1999; censoring occurred at this date or at the last service date, if there was
no record of using services during the last 6 months of follow-up. Crude hazard
ratio and proportional hazard analyses were carried out. RESULTS: 319
patients developed diabetes on olanzapine treatment, and 217 developed
diabetes on risperidone treatment; a crude hazard ratio of 1.08 (95% CI =
0.89 to 1.31, p =.43) was determined. When age, gender, and haloperidol use
were controlled for using proportional hazard analysis, there was a 20%
increased risk of diabetes with olanzapine relative to risperidone (95% CI =
0% to 43%, p =.05). Proportional hazard analyses adjusted for duration of
olanzapine exposure indicated that the first 3 months of olanzapine treatment
was associated with an increased risk of diabetes of 90% (95% CI = 40% to
157%, p <.0001), after adjusting for age, gender, and haloperidol use.
CONCLUSION: Compared with risperidone, olanzapine was associated with an
increased risk of developing diabetes. More studies are required to further
investigate this association. J Clin Psychiatry 2002 Oct;63(10):920-30
:
Differential effects of risperidone, olanzapine, clozapine, and
conventional antipsychotics on type 2 diabetes: findings from a
large health plan database.
Gianfrancesco FD, Grogg AL, Mahmoud RA, Wang RH, Nasrallah HA.
HECON Associates, Montgomery Village, MD 20886, USA. fgian1708@aol.com BACKGROUND: Case series suggest that some antipsychotics may induce or
exacerbate type 2 diabetes. This study measured the association of
antipsychotic treatments with diabetes at a population level. METHOD: Claims
data for psychosis patients (ICD-CM-9 290.xx-299.xx) within health plans
encompassing 2.5 million individuals were analyzed. Patients reporting
preexisting type 2 diabetes up to 8 months prior to observation were excluded.
The frequency of newly reported type 2 diabetes in untreated patients and
among patients treated with antipsychotics from 5 categories (risperidone,
olanzapine, clozapine, and high-potency and low-potency conventionals) was
compared. Logistic regression models compared the odds of diabetes based on
exposure to each of the antipsychotic categories. RESULTS: Based on 12
months of exposure, the odds of type 2 diabetes for risperidone-treated
patients (odds ratio = 0.88, 95% CI = 0.372 to 2.070) was not significantly
different from that for untreated patients, whereas patients receiving other
antipsychotics had a significantly greater risk of diabetes than untreated
patients (p < .05): olanzapine, 3.10 (95% CI = 1.620 to 5.934); clozapine, 7.44
(95% CI = 0.603 to 34.751); high-potency conventionals, 2.13 (95% CI = 1.097
to 4.134); and low-potency conventionals, 3.46 (95% CI = 1.522 to 7.785).
Older age and greater use of non-antipsychotic psychotropic medications also
contributed to risk of type 2 diabetes. Olanzapine also showed significantly
higher (p < .01) odds of diabetes associated with increasing dose.
CONCLUSION: Consistent with previously published literature, these data
suggest that olanzapine, clozapine, and some conventional antipsychotics appear
to increase the risk of acquiring or exacerbating type 2 diabetes and that the
effect may vary by drug. In contrast to these agents, risperidone was not
associated with an increased risk of type 2 diabetes.
Lumiscope 1247 Electronic Pill Timer
Ann Pharmacother 2001 Dec;35(12):1517-22
:
Comment in:
Ann Pharmacother. 2001 Dec;35(12):1659-60.
Risk of extrapyramidal syndromes with haloperidol, risperidone,
or olanzapine.
Schillevoort I, de Boer A, Herings RM, Roos RA, Jansen PA, Leufkens
HG.
Department of Pharmacoepidemiology and Pharmacotherapy, Utrecht Institute
for Pharmaceutical Sciences, PO Box 80082, 3508 TB, Utrecht, The
Netherlands. i.e.r.m.schillevoort@pharm.uu.nl OBJECTIVE: To compare the risk of extrapyramidal syndrome (EPS) between
risperidone, olanzapine, and haloperidol, taking into account patients' past
antipsychotic drug use and past EPS. METHODS: Data were obtained from the
PHARMO-database, containing filled prescriptions of 450,000
community-dwelling people in the Netherlands from 1986 through 1999. We
defined cohorts of first-time users of haloperidol, risperidone, or olanzapine
aged 15 to 54 years. In the first 90 days of treatment, we assessed the
occurrence of EPS, defined as first use of any antiparkinsonian agent. We
estimated relative risks of EPS for risperidone and olanzapine versus
haloperidol using a Cox proportional hazards model. Patients were subdivided
according to prior use of antipsychotic and antiparkinsonian drugs. RESULTS:
We identified 424 patients starting treatment with haloperidol, 243 with
risperidone, and 181 with olanzapine. Prior use of antipsychotic plus
antiparkinsonian medication was significantly more frequent among users of
risperidone and olanzapine than in those using haloperidol (36.2%, 40.3%, and
4.5%, respectively; p < 0.001). Within most subgroups of comparable treatment
history, patients using risperidone and olanzapine showed reduced risks of EPS
compared with haloperidol, although some of these findings did not reach
statistical significance (RR 0.03-0.22). However, this was not observed for
patients using risperidone who had experienced EPS in the past (RR 1.30; 95%
CI 0.24 to 7.18). CONCLUSIONS: In general, we observed reduced risks of
EPS for risperidone and olanzapine compared with haloperidol within subgroups
of patients with a similar treatment history. However, the added value of
risperidone in patients who have experienced EPS in the past needs further
study. J Affect Disord 2003 Jan;73(1-2):147-53
:
Placebo-controlled trials do not find association of olanzapine with
exacerbation of bipolar mania.
Baker RW, Milton DR, Stauffer VL, Gelenberg A, Tohen M.
Lilly Research Laboratories, Eli Lilly and Company, Lilly Corporate Center,
Drop Code 4133, 46285, Indianapolis, IN, USA BACKGROUND: Published case reports describe apparent induction or
exacerbation of manic-like symptoms during treatment with the atypical
antipsychotics olanzapine and risperidone. To date, such reports are from
uncontrolled clinical experience and therefore cannot clarify whether the
atypical antipsychotics caused such manic-like states or simply failed to
prevent them. Presumably, bipolar patients would be at increased risk for this
putative adverse event. Therefore, we evaluated the potential of olanzapine to
exacerbate symptoms of mania compared to placebo during treatment of bipolar
mania. METHODS: Two inpatient, double-blind, randomized trials investigating
the efficacy of olanzapine 5-20 mg daily versus placebo for the treatment of
acute mania were combined. Two hundred and fifty-four subjects participated
(placebo n=129; olanzapine n=125) in the two studies. Severity of mania was
quantified with the 11-item Young-Mania Rating Scale (Y-MRS). In a post-hoc
analysis, after double-blind therapy up to 3 weeks, categorical comparison of
olanzapine and placebo groups was made for any worsening and worsening by 10
or 20% from baseline Y-MRS scores (LOCF). RESULTS: The percentage of
subjects with exacerbation at endpoint were: any worsening, placebo 37.7%,
olanzapine 21.8% (P=0.005); >/=10% worsening, placebo 24.6%, olanzapine
14.5% (P=0.039); >/=20% worsening, placebo 15.6%, olanzapine 8.1% (P=0.064).
CONCLUSION: Mania rating scores worsened for some patients during
olanzapine therapy. However, this was significantly less common with olanzapine
than with placebo. These controlled data suggest that clinical case reports of
occurrence of 'mania' during treatment with olanzapine, and possibly those with
other atypical antipsychotics, reflect exacerbation in the natural history of
bipolar illness, rather than an adverse pharmacological effect.
LIMITATIONS: Post-hoc analysis of pooled data from two different studies. Expert Opin Pharmacother 2002 Dec;3(12):1773-81
:
Aripiprazole: profile on efficacy and safety.
Goodnick PJ, Jerry JM.
D79, University of Miami School of Medicine, 1400 NW 10 Avenue, Ste 304A,
Miami, FL 33136, USA. pgoodnick@aol.com Aripiprazole (Abilitat trade mark, Bristol-Myers Squibb) is the most recent
addition to the new class of atypical antipsychotic medications, following the
release of clozapine, risperidone, olanzapine, quetiapine and ziprasidone.
Aripiprazole exhibits typical antagonism at dopamine (D2) receptors in the
mesolimbic pathway, as well as having unique partial agonist activity at D2
receptors in the mesocortical pathway. As exemplified by other atypical
antipsychotics, it displays strong 5-HT(2a) receptor antagonism and is similar
to ziprasidone in also having agonistic activity at the 5-HT(1a) receptor. Among
the atypical antipsychotics, aripiprazole displays the lowest affinity for
alpha(1)adrenergic (alpha(1)), histamine (H1) and muscarinic (M1) receptors.
This combination of effects may be responsible for its efficacy in positive and
negative symptoms of schizophrenia and in bipolar disorder. Similarly, this
profile may be the reason for the low rates of reported side effects observed.
This includes general adverse events, a low incidence of reported weight gain
and a low liability for inducing movement disorders. Other early data suggest
that aripiprazole may induce reductions in plasma prolactin, as well as in plasma
glucose and lipid profiles. Finally, results also support the proposition that
aripiprazole may lead to reductions in corrected QT interval and have minimal
drug interactions.: Schizophr Res 2003 Jan 1;59(1):1-6 :
New-onset diabetes and ketoacidosis with atypical antipsychotics.
Wilson DR, D'Souza L, Sarkar N, Newton M, Hammond C.
Department of Psychiatry, Creighton University School of Medicine, Omaha, NE, USA
Information from the Ohio Department of Mental Health (ODMH) database was reviewed retrospectively to identify patients at the Cincinnati center treated with an atypical antipsychotic and who had also been evaluated or treated for diabetes mellitus. Blood glucose levels, glucose tolerance, or other evaluations of diabetes had been conducted in 14 of the 126 patients treated with atypical antipsychotics. In 11 of the 14, new-onset, acute, and marked glucose intolerance developed after treatment with clozapine, olanzapine or quetiapine. Of these, six patients required insulin therapy (four only transiently) and five patients developed diabetic ketoacidosis (DKA). Also, glucose metabolism was labile in all cases, and was transient in two cases with subsequent resolution despite on-going antipsychotic therapy. Certain atypical antipsychotics may be associated with new-onset glucose intolerance, including acute diabetes and ketoacidosis. Monitoring for changes in blood glucose levels in patients taking atypical antipsychotics may be indicated. More systematic study data are clearly needed: Ann Pharmacother 2002 Dec;36(12):1875-8 :
Quetiapine therapy for posttraumatic stress disorder.
Sattar SP, Ucci B, Grant K, Bhatia SC, Petty F.
S Pirzada Sattar MD, Assistant Professor of Psychiatry, School of Medicine, Creighton University; Director, Psychiatric Services, Substance Abuse Treatment Center, Omaha Veterans Affairs Medical Center, Omaha, NE OBJECTIVE: To report a case of improvement in posttraumatic stress disorder (PTSD) after adjunctive therapy with quetiapine. CASE SUMMARY: A 49-year-old white man witnessed a traumatic event and experienced severe PTSD. He was started on paroxetine, with increases in dosage and no significant improvement. Quetiapine was added to his regimen, with increased doses resulting in improvement of PTSD symptoms, both clinically and as measured on the Hamilton-D rating scale for depression and the clinician-administered PTSD screen. DISCUSSION: This is the first case published in the English language literature describing improvement in PTSD symptoms after treatment with quetiapine. There are several treatment options for PTSD, but some severe cases may require treatment with antipsychotic medications. Because of the lower risks of serious adverse effects, the newer atypical antipsychotics are much safer than the older antipsychotics. Although use of risperidone and olanzapine in the successful treatment of PTSD has been reported in the literature, there are no reports of quetiapine use in this clinical condition. CONCLUSIONS: Quetiapine appeared to improve clinical signs and symptoms of PTSD in this patient. It may be a treatment option in other severe cases of PTSD.
: Expert Opin Pharmacother 2002 Dec;3(12):1773-81 :
Aripiprazole: profile on efficacy and safety.
Goodnick PJ, Jerry JM.
D79, University of Miami School of Medicine, 1400 NW 10 Avenue, Ste 304A, Miami, FL 33136, USA. pgoodnick@aol.com
Aripiprazole (Abilitat trade mark, Bristol-Myers Squibb) is the most recent addition to the new class of atypical antipsychotic medications, following the release of clozapine, risperidone, olanzapine, quetiapine and ziprasidone. Aripiprazole exhibits typical antagonism at dopamine (D2) receptors in the mesolimbic pathway, as well as having unique partial agonist activity at D2 receptors in the mesocortical pathway. As exemplified by other atypical antipsychotics, it displays strong 5-HT(2a) receptor antagonism and is similar to ziprasidone in also having agonistic activity at the 5-HT(1a) receptor. Among the atypical antipsychotics, aripiprazole displays the lowest affinity for alpha(1)adrenergic (alpha(1)), histamine (H1) and muscarinic (M1) receptors. This combination of effects may be responsible for its efficacy in positive and negative symptoms of schizophrenia and in bipolar disorder. Similarly, this profile may be the reason for the low rates of reported side effects observed. This includes general adverse events, a low incidence of reported weight gain and a low liability for inducing movement disorders. Other early data suggest that aripiprazole may induce reductions in plasma prolactin, as well as in plasma glucose and lipid profiles. Finally, results also support the proposition that aripiprazole may lead to reductions in corrected QT interval and have minimal drug interactions.
: Hum Psychopharmacol 2002 Dec;17(8):407-12 :
Pharmacotherapy of bipolar disorder: the role of atypical antipsychotics and experimental strategies.
Malhi GS, Berk M.
The University of New South Wales Mood Disorders Unit, The Black Dog Institute, The Villa, Prince of Wales Hospital, Randwick, Sydney, NSW 2031, Australia.
Bipolar disorder, despite being a common and debilitating illness, has remarkably few pharmacological therapeutic options, the majority of which, with the exception of lithium, have been borrowed from other medical indications. Furthermore the quantity and quality of controlled clinical data are considerably smaller than in conditions of comparable severity and frequency. Not surprisingly, the clinical outcome of bipolar disorder is frequently suboptimal.Fortunately there are a growing number of novel therapeutic options for its treatment such as atypical antipsychotics, calcium channel blockers and omega-3 fatty acids. This paper summarizes some of the data regarding these 'experimental' therapeutic options, focusing principally on atypical antipsychotics as these are now widely prescribed in the management of bipolar disorder : Mol Psychiatry 2002;7 Suppl 1:S29-34
:
Synaptic plasticity and mood disorders.
Duman RS.
Division of Molecular Psychiatry, Abraham Ribicoff Research Facilities,
Connecticut Mental Health Center, Yale University School of Medicine, New
Haven, CT, USA. ronald.duman@yale.edu Recent studies demonstrate that the molecular elements known to regulate
neuronal plasticity in models of learning and memory are also involved in the
actions of drugs used for the treatment of depression and bipolar disorder.
This includes up-regulation of transcription factors, such as the cAMP response
element binding protein and neurotrophic factors, such as brain derived
neurotrophic factor. These findings raise the possibility that regulation of
neural plasticity in specific neuronal circuits is integrally involved in the
therapeutic intervention of mood disorders. Atypical antipsychotic drugs,
including clozapine and olanzapine, are also effective for the treatment of
bipolar disorder, and are used as add-on medication for unipolar depression.
The possibility that these atypical antipsychotic drugs also influence the
molecular determinants of synaptic plasticity that are involved in the response
to drugs used for the treatment of mood disorders, is discussed.Atypical antipsychotics in the treatment of bipolar affective disorders
Antipsychotics are commonly used in the treatment of bipolar affective disorder. The use of
conventional antipsychotic agents, though effective as antimanic agents, is associated with a
number of limitations such as their acute side effect profile and their unsufficient mood stabilizing
activity. In addition, exposure to conventional neuroleptics poses a risk for the development of
tardive dyskinesia, especially in mood disorder patients. Growing evidence suggests that the
novel, so-called atypical neuroleptics may offer a number of advantages in the treatment of
bipolar disorder, including their thymoleptic activity and minimal risk for acute and long-term
extraypyramidal symptoms. Clinical experience with clozapine and olanzapine as mood
stabilizers suggests greater antimanic than antidepressant properties, while risperidone may have
greater antidepressant properties with some liability for triggering or exacerbating mania. The
mood stabilizing properties of further atypical drugs are currently under investigation. This
review focuses on the use of atypical antipsychotics in the treatment of bipolar disorder. We
also present an overview concerning potential pharmakokinetic interactions based on the
cytochrome P450 enzyme system when antipsychotics are combined with other mood stabilizing
compounds. In conclusion, atypical antipsychotics should come to play an increasingly important
role in the acute and long-term management of bipolar disorder, but there is a clear need for
further controlled trials in this indication Atypical antipsychotics in the treatment of bipolar affective disorders] Antipsychotics are commonly used in the treatment of bipolar affective disorder. The use of
conventional antipsychotic agents, though effective as antimanic agents, is associated with a
number of limitations such as their acute side effect profile and their unsufficient mood stabilizing
activity. In addition, exposure to conventional neuroleptics poses a risk for the development of
tardive dyskinesia, especially in mood disorder patients. Growing evidence suggests that the novel,
so-called atypical neuroleptics may offer a number of advantages in the treatment of bipolar
disorder, including their thymoleptic activity and minimal risk for acute and long-term
extraypyramidal symptoms. Clinical experience with clozapine and olanzapine as mood stabilizers
suggests greater antimanic than antidepressant properties, while risperidone may have greater
antidepressant properties with some liability for triggering or exacerbating mania. The mood
stabilizing properties of further atypical drugs are currently under investigation. This review focuses
on the use of atypical antipsychotics in the treatment of bipolar disorder. We also present an
overview concerning potential pharmakokinetic interactions based on the cytochrome P450 enzyme
system when antipsychotics are combined with other mood stabilizing compounds. In conclusion,
atypical antipsychotics should come to play an increasingly important role in the acute and long-term
management of bipolar disorder, but there is a clear need for further controlled trials in this
indication.Psychopharmacological treatment of bipolar disease] This paper gives an update on the psychopharmacological treatment of bipolar disorder. The
antimanic efficacy of lithium is well documented. The same applies to valproate, which is also
efficacious in mixed mania. Conventional antipsychotics act fast in mania and do not require blood
tests, but they have considerable neurological side effects. The newer antipsychotics, olanzapine,
risperidone, and ziprasidone, have also been shown to have antimanic efficacy. Clozapine is
extremely effective, also when other treatment fails. For the treatment of bipolar depression,
lithium, lamotrigine, and antidepressants all seem to work, but antidepressants may sometimes
precipitate mania or worsen the course of illness. For prophylaxis, lithium is still to be considered the
first drug of choice. However, for several reasons, for instance treatment failure or side effects,
long-term treatment with antiepileptics may often be necessary. Among the antiepileptics,
carbamazepine, valproate, and lamotrigine are the best studied.The role of novel antipsychotics in bipolar disorders.
Patients with bipolar disorder frequently receive antipsychotic agents during both the acute and
maintenance phases of treatment. Conventional antipsychotics are effective against mania, but they
may induce depressive symptoms and expose patients with bipolar disorder to increased risks of
tardive dyskinesia. Recent studies have shown risperidone to be effective for acute mania, both as
monotherapy and in combination with mood stabilizers; this agent has also shown efficacy as
add-on maintenance therapy in open-label studies as it exhibited both antimanic and antidepressant
effects. Olanzapine, another novel antipsychotic, is also effective against both manic and depressive
symptoms and in the maintenance treatment as indicated by an open-label study. Data on other
novel agents are more limited./The role of novel antipsychotics in bipolar disorders Patients with bipolar disorder frequently receive antipsychotic agents during both the acute and
maintenance phases of treatment. Conventional antipsychotics are effective against mania, but
they may induce depressive symptoms and expose patients with bipolar disorder to increased
risks of tardive dyskinesia. Recent studies have shown risperidone to be effective for acute
mania, both as monotherapy and in combination with mood stabilizers; this agent has also shown
efficacy as add-on maintenance therapy in open-label studies as it exhibited both antimanic and
antidepressant effects. Olanzapine, another novel antipsychotic, is also effective against both
manic and depressive symptoms and in the maintenance treatment as indicated by an open-label
study. Data on other novel agents are more limited.E-Utilities
Optimal dosing of atypical antipsychotics in adults: a review of the
current evidence
This review describes dosing strategies used to optimize the beneficial effects of atypical
antipsychotic medications. Differences between manufacturers' recommended dosing and actual
clinical practice are reconciled using evidence from pivotal double-blind randomized registration
studies, other randomized clinical trials, case series, and case reports. With clozapine and
perhaps olanzapine, plasma levels are correlated with therapeutic response; with risperidone,
plasma levels are not correlated with therapeutic response but may be related to the occurrence
of extrapyramidal symptoms. Information related to optimal dosing of quetiapine and
ziprasidone is more limited. In clinical practice, the mean daily dose of risperidone has
decreased, whereas that for olanzapine is increasing. The percentage of patients receiving
quetiapine at doses above the manufacturer's recommended maximum is higher than would be
expected, further illustrating that dosing ranges established during registration studies may not
reflect the needs of day-to-day practiceBody weight changes associated with psychopharmacology.
OBJECTIVE: The authors discuss changes in body weight associated with various
psychopharmaceuticals. METHODS: A large number of articles and books about drug-induced
changes in body weight, selected on the basis of various literature searches and the authors'
clinical experiences with psychopharmaceuticals, were reviewed. RESULTS: Many
psychotropic drugs with antipsychotic, mood stabilizing, and antidepressant properties are
associated with weight gain. Others, such as fluoxetine, isocarboxazid, nefazadone, topiramate,
and psychostimulants, may cause weight loss. The antipsychotic drugs chlorpromazine,
clozapine, and olanzapine are often associated with weight gain. Among antidepressants,
amitriptyline and mirtazapine are known to cause weight gain. However, reductions are
sometimes observed, and each antidepressant has its own unique weight-effect profile. Mood
stabilizers, especially valproate-related products, are also associated with weight gain.
CONCLUSIONS: Careful monitoring and consideration of alternative therapies are essentialJ Affect Disord 2003 Jan;73(1-2):75-85
:
Duration and stability of the rapid-cycling course: a long-term
personal follow-up of 109 patients.
Koukopoulos A, Sani G, Koukopoulos AE, Minnai GP, Girardi P, Pani L, Albert
MJ, Reginaldi D.
Centro Lucio Bini-Roma, Via Crescenzio 42, 00193, Rome, Italy BACKGROUND: Recognition by the DSM-IV of rapid cyclicity as a course specifier
has raised the question of the stability and long-term outcome of rapid-cycling (RC)
patients. Data on this topic is sparse and often inconsistent. To our knowledge,
these are the first personally followed patients over the long term, dealing directly
with the issue of the duration of the RC course. METHODS: We examined the
evolution of the course of 109 RC patients (68 women and 41 men) followed for a
minimum of 2 years and up to 36 years, beginning with the index episode when the RC
course was diagnosed by the authors (A.K., G.P.M., P.G., L.P., D.R.). Patients were
included in the study if they met criteria for RC as defined by>/=4 affective
episodes per year (). The follow-up period varied from 2-5 years for 25 patients,
6-10 years for 24 patients, 11-15 years for 24 patients, 16-20 years for 19 patients,
21-25 years for 13 patients, 30-36 years for four patients. RESULTS: In 13 patients
(12%), RC emerged spontaneously and in 96 patients (88%), it was associated with
antidepressant and other treatments. In 19 women (28% of all women) RC course
started in perimenopausal age (45-54 years). The mean duration of RC during the
follow-up period was 7.86 years (range 1-32) and its total duration (including RC
course prior to the follow-up period) was 11 years (range 1-40). The total duration
of the affective disorder, from the first episode to the end of the follow-up, was
21.78 years (range 1-70). At the end of the follow-up, 36 patients (33%) had
complete remission for at least the past year, 44 (40%) stayed rapid cycling with
severe episodes (six of this group committed suicide), while 15 (14%) were rapid
cycling but with attenuated episodes. The other 14 patients (13%) became long
cyclers, eight with severe episodes and six with milder ones. The main distinguishing
features between those who remitted from and those who persisted in the RC
course were: (1) the initial cycle pattern: patients with
Depression-Hypomania(mania)-Free interval cycles (53 patients) had a worse
outcome: 26.4% remitted and 52.8% persisted in the RC course through to the end
of the follow up period. The Mania/Hypomania-Depression-Free interval cycles (22
patients) had a significantly better outcome, with 50% remitted and 27.2%
persisting RC; and (2) the occurrence of the switch process from depression to
hypomania/mania and the occurrence of agitated depressions made the prognosis
worse. Continuous treatment was more effective against mania/hypomania than
against depression, yet in all persisting RC cases the mania/hypomania remitted only
partially. LIMITATIONS: These data derive from clinics known for their expertise
in mood disorders, and they may have attracted and retained patients with a more
severe course. Treatment was uncontrolled and consisted more of lithium than
divalproex, lamotrigene and olanzapine, recently shown to be beneficial in subgroups
of patients with rapid-cycling. CONCLUSIONS: Our findings suggest that rapid
cyclicity, spontaneous or induced, once established, becomes for many years a
stable rhythm in a substantial proportion of patients, linked to endogenous and
environmental factors. The suggestion is made to consider as rapid-cyclers, at least
for research purposes, those patients who have had a rapid cycling course for at
least 2 years, borrowing the duration criterion currently employed for other chronic
disorders such as Dysthymia and Cyclothymia. That our patients had poorer
prognosis than some other cohorts in the literature is probably due to the shorter
duration of "rapid-cycling" at entry in the latter cohorts. A true understanding of
the nature of rapid-cycling will require a rigorous definition of not only duration,
but also pole-switching and course patterns at entry into study.J Affect Disord 2003 Jan;73(1-2):155-61
Related Articles, Links
Olanzapine in the acute treatment of bipolar I disorder with a
history of rapid cycling.
Sanger TM, Tohen M, Vieta E, Dunner DL, Bowden CL, Calabrese JR, Feldman
PD, Jacobs TG, Breier A.
Lilly Research Laboratories, 46285, Indianapolis, IN, USA BACKGROUND: A substantial proportion of patients with bipolar disorder are
characterized by a rapidly cycling course and are particularly resistant to
conventional treatment. METHODS: This secondary analysis, defined a priori, was
conducted on a larger data set from patients with bipolar I disorder to determine
the efficacy of a 3-week treatment with the atypical antipsychotic olanzapine
(5-20 mg/day, n=19) versus placebo (n=26) in patients with >/=4 episodes in the
preceding year. RESULTS: Significantly fewer placebo patients completed
treatment (34.6 vs. 73.7%, P=0.016), and more than half discontinued due to lack of
efficacy (53.8 vs. 21.1%, P=0.035). Olanzapine reduced Young Mania Rating Scale
(YMRS) total scores significantly more than placebo (-13.9 vs. -4.1, P=0.011). Clinical
responses, defined as >/=50% improvement in YMRS, were achieved in 58% of
olanzapine patients, compared with 28% of placebo patients (P=0.066).
Extrapyramidal symptoms were not significantly changed in either group.
Somnolence was the most common adverse event in both groups (olanzapine: 52.6%,
placebo: 23.1%; P=0.060). No event occurred significantly more frequently with
olanzapine than with placebo. No patients discontinued due to an adverse event.
LIMITATIONS: The duration of this study was limited to 3 weeks, precluding
conclusions about long-term efficacy of olanzapine. Moreover, a sizeable placebo
effect was obtained, possibly masking optimal therapeutic effect. Despite these
limitations, treatment differences in efficacy were highly significant.
CONCLUSIONS: These results indicate that olanzapine was effective in reducing
symptoms of mania and well tolerated in patients with bipolar I disorder with a
rapid-cycling course.
1: J Clin Psychopharmacol 2001 Oct;21(5):469-73
Related Articles, Links
Olanzapine as long-term adjunctive therapy in treatment-resistant bipolar
disorder. The aim of this study was to estimate the long-term effectiveness of olanzapine as adjunctive
therapy in patients with bipolar disorder who exhibited an inadequate response to mood
stabilizers. Twenty-three Research Diagnostic Criteria (RDC) patients with bipolar I and II
were assessed by means of the Schedule for Affective Disorders and Schizophrenia and entered
if they gave their consent to participate. All of them had experienced frequent relapses, residual
subsyndromal symptoms, and inadequate responses to other drugs, such as lithium, valproate,
or carbamazepine. While maintaining other drugs, they all received open-label, increasing doses
of olanzapine, until achieving clinical response. Other drugs were maintained. The patients were
assessed several consecutive times from baseline to the endpoint with the Clinical Global
Impressions (CGI) scale for use in bipolar illness. Records of recurrences, hospitalizations, and
side effects were also collected. The last-observation-carried-forward analysis showed that
there was a significant reduction of CGI scores after the introduction of olanzapine, either in
manic symptoms (p = 0.0015), depressive symptoms (p = 0.0063), or global symptoms (p =
0.0003). The most frequent adverse events were somnolence (17%) and weight gain (13%).
The mean dose of olanzapine at the end of the 43-week follow-up was 8.1 mg/day. Olanzapine
may be a useful medication for the long-term adjunctive treatment of patients with bipolar
disorder who exhibit a poor response to mood stabilizers, such as lithium, valproate, or
carbamazepine. These results suggest mood-stablizing properties of olanzapine. Bipolar Disord 2002 Oct;4(5):335-40
:
Quetiapine in the treatment of rapid cycling bipolar disorder.
Vieta E, Parramon G, Padrell E, Nieto E, Martinez-Aran A, Corbella B,
Colom F, Reinares M, Goikolea JM, Torrent C.
Bipolar Disorders Program, Hospital Clinic, University of Barcelona, Barcelona.
Spain. evieta@clinic.ub.es INTRODUCTION: This prospective open-label study assessed the impact of
add-on quetiapine in the treatment of rapid cycling bipolar patients.
METHODS: Fourteen rapid cycling bipolar patients were treated with
quetiapine, which was added to their ongoing medication regimen for 112 +/- 33
days. At the beginning of the study, five were manic, three were in a mixed
state, three were depressed, two hypomanic and one was euthymic. Patients were
assessed prospectively with a modified version of the Clinical Global Impression
Scale for Bipolars (CGI-BP), the Young Scale for mania (YMRS) and the
Hamilton Scale for Depression (HDRS). RESULTS: A significant reduction of
the following scale scores was observed: a 1.8 point reduction for the general
CGI-BP (p = 0.013), a -1.3 point for the mania subscale (p = 0.016), a -1.01 point
for the YMRS (p = 0.025). Improvement in depressive symptoms was not
significant, neither in the CGI-BP (-1 point, p = 0.074) nor in the HDRS (-5.2
points, p = NS). The most common side-effect was sedation (n = 6, 43%). Doses
of quetiapine were significantly reduced by the end of the study (443 +/- 235
mg/day versus 268 +/- 190 mg/day, p = 0.008) and they also differed
according to the initial episode to be treated (720 +/- 84 mg/day for mania,
and 183 +/- 29 mg/day for depression, p = 0.023). CONCLUSIONS:
Quetiapine could possibly be an effective treatment for rapid cycling bipolar
patients. Adequate doses for acute episodes could significantly differ according
to the episode polarity and the length of treatment Ann Pharmacother 2002 Dec;36(12):1875-8
:
Quetiapine therapy for posttraumatic stress disorder.
Sattar SP, Ucci B, Grant K, Bhatia SC, Petty F.
S Pirzada Sattar MD, Assistant Professor of Psychiatry, School of Medicine,
Creighton University; Director, Psychiatric Services, Substance Abuse Treatment
Center, Omaha Veterans Affairs Medical Center, Omaha, NE. OBJECTIVE: To report a case of improvement in posttraumatic stress disorder
(PTSD) after adjunctive therapy with quetiapine. CASE SUMMARY: A 49-year-old
white man witnessed a traumatic event and experienced severe PTSD. He was
started on paroxetine, with increases in dosage and no significant improvement.
Quetiapine was added to his regimen, with increased doses resulting in
improvement of PTSD symptoms, both clinically and as measured on the
Hamilton-D rating scale for depression and the clinician-administered PTSD
screen. DISCUSSION: This is the first case published in the English language literature describing improvement in PTSD symptoms after treatment with quetiapine. There are several treatment options for PTSD, but some severe cases may require treatment with antipsychotic medications. Because of the lower risks of serious adverse effects, the newer atypical antipsychotics are much safer than the older antipsychotics. Although use of risperidone and olanzapine in the successful treatment of PTSD has been reported in the literature, there are no reports of quetiapine use in this clinical condition. CONCLUSIONS: Quetiapine appeared to improve clinical signs and symptoms of PTSD in this patient. It may be a treatment option in other severe cases of PTSD.
Anorexia Nervosa
Int J Eat Disord 2003 Jan;33(1):98-103
:
Olanzapine use as an adjunctive treatment for hospitalized
children with anorexia nervosa: Case reports.
Boachie A, Goldfield GS, Spettigue W.
Department of Psychiatry, Children's Hospital of Eastern Ontario, Ottawa, Canada. OBJECTIVE: A recent case report suggested that olanzapine resulted in improved
weight gain and maintenance, as well as decreased anxiety and agitation, for two
hospitalized inpatients with anorexia nervosa (AN). However, a subsequent larger
case study did not show a relationship between the use of olanzapine and rate of
weight gain among a primarily adult population. The aim of this case report was to
clinically examine the therapeutic benefit and tolerability of olanzapine as an
adjunctive treatment for four children with AN in a pediatric inpatient setting.
RESULTS: Olanzapine use was associated with considerable weight gain and
maintenance, with an average rate of weight gain during hospitalization of 0.99 kg
per week. In addition to weight gain, olanzapine was associated with a clinically
notable decrease in levels of agitation and premeal anxiety and almost immediate
improvement in sleep, general functioning, and overall compliance with treatment.
Olanzapine was also well tolerated in these young patients. DISCUSSION: These
case report findings warrant more controlled research, including randomized
controlled studies, to better determine the therapeutic benefits and safety of
olanzapine use in children with AN.
Atypical Antipsychotics for Obsessive complusives
Int Clin Psychopharmacol 2003 Jan;18(1):23-8
:
Antipsychotic augmentation for treatment resistant
obsessive-compulsive disorder: what if antipsychotic is
discontinued?
Maina G, Albert U, Ziero S, Bogetto F. The aim of the present study was to retrospectively review the charts of
obsessive-compulsive disorder (OCD) patients who responded to the addition of
an antipsychotic to the seroronin reuptake inhibitor (SRI), and who
subsequently discontinued the antipsychotic, in order to evaluate whether
antipsychotic discontinuation resulted in a relapse of the disorder. Charts of
patients with a principal diagnosis of OCD (DSM-IV) treated with
pharmacotherapy were reviewed in order to select patients who: (i) did not
respond to a trial with a first-line drug (clomipramine or a selective SRI); (ii)
received an antipsychotic at low doses (haloperidol, pimozide, risperidone or
olanzapine) in order to potentiate the SRI; (iii) responded to this augmentation
strategy; and (iv) discontinued the antipsychotic drug for any reason while
continuing the SRI at the same dose. Relapse was defined as a worsening of
Yale-Brown Obsessive-Compulsive Scale (Y-BOCS) total score >/= 35% with
respect to last evaluation before antipsychotic discontinuation or, for patients
with a Y-BOCS < 16 at the end of the combination period, as a Y-BOCS total
score >/= 16 at any time after antipsychotic discontinuation. According to our
definition of relapse, 15 patients out of 18 (83.3%) relapsed after
antipsychotic discontinuation, with a mean worsening of symptoms of 6.6 +/- 1.7
points in the Y-BOCS total score. Thirteen patients out of the 15 who relapsed
did so by week 8 after discontinuation. Two subjects relapsed at the end of the
1-year study. Although retrospective, our study provides initial evidence that
antipsychotic augmentation has to be maintained for patients who respond to
this strategy, because the vast majority of subjects who discontinue the
antipsychotic relapse within 2 months.
Atypical Antipsychotics for Schizophrenia
Eur Neuropsychopharmacol 2003 Jan;13(1):39-48
:
Safety of olanzapine versus conventional antipsychotics in the
treatment of patients with acute schizophrenia. A naturalistic
study.
Alvarez E, Bobes J, Gomez JC, Sacristan JA, Canas F, Carrasco JL, Gascon
J, Gibert J, Gutierrez M.
Hospital de la Santa Creu i Sant Pau, Autonomous University of Barcelona,
Barcelona, Spain BACKGROUND: Conventional antipsychotics although effective in treating acute
psychotic and behavioural symptoms are subject to certain limitations due to the
high incidence of side effects associated, mainly extrapyramidal symptoms (EPS),
and insufficient response shown in some cases. EPS are a major factor in neuroleptic
non compliance and high relapse rates among patients. This study was designed to
assess the safety and effectiveness of olanzapine compared to typical
antipsychotics drugs in the treatment of schizophrenic inpatients at acute
psychiatric in-patient units. METHOD: Data from 904 patients schizophrenic
patients (F20 of ICD10, WHO) were collected in this prospective, comparative,
non-randomized, open and observational study. Patients were followed during their
entire hospital stay. Safety was assessed through the collection of spontaneous
adverse events and a specific extrapyramidal symptoms questionnaire (EPS). Clinical
status was measured through the Brief Psychiatric Rating Scale (BPRS), Clinical
Global Impression of Severity (CGI-S), Patient Global Impression of Improvement
(PGI) and the Nursing Observational Scale for In-patient Evaluation (NOSIE).
RESULTS: A total of 483 patients received olanzapine (olanzapine group, OG), and
421 received typical antipsychotics (control group, CG). Treatment emergent EPS, or
worsening of previous EPS were statistically significantly higher in the CG (P=0.001).
Responder rate was statistically greater in the OG (P<0.001). Mean change in
BPRS-total, BPRS-negative, BPRS-agitation subscales and PGI was significantly
higher in the OG (P<0.001). Mean decrease in CGI, BPRS positive and BPRS
depression sub-scales was also significantly lower (P</
