antipsychotics and depression
There is a growing interest in research for the effect of antipsychotics and depression. This webpage will present the latest research abstracts dealing with the affects of antipsychotics and depression. Many people who are bipolar are given antipsychotics for mania besides schizophrenics who are given antipsychotics. Bipolars suffer from depression and many suffer from treatment resistant depression where antidepressants along with mood stabilizers do not work. Some studies suggest that antipsychotics can help with the treatment resistant depression. Obviously there needs to be more research. These articles have been collected by a bipolar II person on Abilify and Seroquel, two atypical antipsychotics. The Seroquel replaced the Risperdal, another antipsychotic, because of its sleep properties.
Abilify is one of the few atypical antipsychotics that is weight neutral. For instance, Ziprexa can cause situational depression because one can gain so much weight! More doctors are opting for Geodon over Zyprexa.
1: Int Clin Psychopharmacol. 2005 Jan;20(1):9-11. : Aripiprazole as an augmentor of selective serotonin reuptake inhibitors in depression and anxiety disorder patients. Worthington JJ 3rd, Kinrys G, Wygant LE, Pollack MH.
aCenter for Anxiety and Traumatic Stress Disorders, Massachusetts General Hospital, Boston, Massachusetts cDepartment of Psychiatry, Harvard Medical School, Boston, Massachusetts, USA bAnxiety Disorders Research Program, Cambridge Health Alliance, Cambridge, Massachusetts.
More than half of anxiety and depression patients treated with an adequate course of antidepressants fail to fully improve. We retrospectively examined whether treatment-resistant depression and anxiety disorder patients responded to and tolerated augmentation with the atypical antipsychotic, aripiprazole. We report on patients with depression and anxiety disorders, including panic disorder, generalized anxiety disorder, social anxiety and post-traumatic stress disorder, who had an incomplete response to a variety of selective serotonin reuptake inhibitors (SSRIs) and who received augmentation with aripiprazole. The primary outcome measure was the Clinical Global Impression of Improvement (CGI-I). In the intent-to-treat analysis, the mean+/-SD CGI-S was 3.8+/-1.3 at endpoint. Fifty-nine percent of subjects received CGI-I ratings of 1 or 2, 'much improved' or 'very much improved,' in terms of their depression and anxiety symptoms at the end of 12 weeks. Several patients showed an early (weeks 1-5), as well as sustained, response to augmentation with doses of aripiprazole between 15 and 30 mg/day. The results suggest that aripiprazole may be effective as an augmentation for patients with persistent depressive and anxiety disorders despite initial SSRI treatment. Because this is a retrospective case review, further prospective studies are required to confirm these findings.
Curr Psychiatry Rep. 2004 Dec;6(6):422-4.: The effectiveness of atypical antipsychotic medications in depressive disorders.
Ishak WW, Rapaport MH, Gotto JG.
Department of Psychiatry, Cedars Sinai Medical Center and University of California at Los Angeles, 8730 Alden Drive, Thalians C-301, Los Angeles, CA 90048, USA
Clinical evidence supporting the use of atypical antipsychotic medication (broad-spectrum psychotropic agents) in the treatment of depressive disorders is increasing rapidly. Animal models suggest that when atypical antipsychotic medications are used in combination with a selective serotonin reuptake inhibitor there is additional activation of frontal dopaminergic and noradrenergic neurotransmitter systems. This stimulated the initiation of several clinical trials that showed the efficacy of atypical antipsychotic medication augmentation of selective serotonin reuptake inhibitors for patients with treatment-resistant depression. There also are few case reports of successful treatment of depression with atypical antipsychotic medication alone. When a clinician is treating a depressed patient who did not achieve relief after trials with two different antidepressant regimens, one option to consider is augmentation with an atypical antipsychotic medication to ameliorate depressive symptoms
Ann Clin Psychiatry. 2004 Jan-Mar;16(1):3-13. : Atypical antipsychotics in the treatment of affective symptoms: a review.
Masan PS.
Department of Psychiatry, Duke University Medical Center, Durham, North Carolina 27702-3319, USA.
masan001@mc.duke.edu
Atypical antipsychotics have demonstrated beneficial effects on affective symptoms, in addition to antipsychotic activity. Consequently, their role in the treatment of bipolar disorder and treatment-resistant or psychotic depression has been explored. Adjunctive atypical antipsychotic therapy appears to benefit patients experiencing manic episodes of bipolar disorder, and some studies suggest that monotherapy may also be efficacious. Clinical studies of patients with schizoaffective disorder and major depression support the use of atypical antipsychotics to treat depression. This review focuses on risperidone, olanzapine, quetiapine, and ziprasidone and provides evidence that these drugs demonstrate activity against manic episodes of bipolar disorder when used as adjunctive therapy and possibly as monotherapy and that depression in patients with schizoaffective disorder also responds to these agents
J Nerv Ment Dis. 2004 Sep;192(9):602-6.: Depression with versus without manic features in rapid-cycling bipolar disorder.
Goldberg JF, Wankmuller MM, Sutherland KH.
Bipolar Disorders Research Program, Department of Psychiatry Research, Zucker Hillside Hospital, North Shore Long Island Jewish Health System, Glen Oaks, NY 11004, USA.

Depression has been identified as a hallmark feature of rapid-cycling bipolar disorder, although less attention has been paid to the presence of manic features accompanying depression in rapid cyclers. To provide greater information about the extent to which depression arises with or without salient manic features in rapid cycling, we conducted a preliminary study of rapid cycling in outpatients seeking treatment at an academic specialty center for bipolar disorder. Forty DSM-IV affectively symptomatic bipolar outpatients with past year DSM-IV rapid cycling underwent systematic evaluation of symptoms and illness characteristics. Manic and depressive symptoms, treatments, and clinical features were rated by standardized scales. Major depression was present in most rapid cyclers (85%), but salient manic features were also evident in half of all depressed rapid cyclers. A lifetime history of suicide attempts was significantly more common in rapid cyclers who presented with major depression plus salient manic features than in those who presented with pure depression or pure mania (p = .033). Antidepressants were being prescribed for approximately one third of depressed rapid cycling patients regardless of the presence of concomitant manic features, whereas mood stabilizers tended to be used less often when manic features accompanied depression. Depression in conjunction with manic symptoms, rather than pure depression alone, may be more common among rapid-cycling bipolar patients who seek treatment. Lifetime suicide risk may be greater among rapid cycling patients whose depression occurs in tandem with manic symptoms. Prescribing habits in the community that favor antidepressants over mood stabilizers may promote further mood destabilization in this population. Further studies with larger sample sizes are needed to affirm these provisional findings.
Schizophr Res. 2004 Sep 1;70(1):69-80.: Effects of typical and atypical antipsychotic drugs on maternal behavior in postpartum female rats.
Li M, Davidson P, Budin R, Kapur S, Fleming AS.
Centre for Addiction and Mental Health, The Clarke Division of CAMH, PET Centre, Clarke Site, 250 College Street, Toronto, Ontario M5T 1T8, Canada.
Understanding the effects of antipsychotic drugs (APDs) on social behaviors such as maternal behavior is valuable for understanding the complete spectrum of therapeutic and side-effects of antipsychotics. Although previous studies have suggested that typical antipsychotics impair maternal behavior, the effects of the atypical antipsychotics have not been systematically explored. The purpose of the present report was to examine the effects of typical (haloperidol, HAL) and several atypical (clozapine, CLZ; risperidone, RIS; quetiapine, QUE) antipsychotics on maternal behavior in female rats. Maternal behaviors were examined repeatedly over a period of 24 h after a single injection of a range of doses of HAL, CLZ, RIS or QUE on Day 6 postpartum. All antipsychotic drugs, typical or atypical, elicited a qualitatively similar disruptive effect on the active components of maternal behavior such as pup approach, pup retrieval and nest building at clinically relevant doses. However, HAL caused a prolonged disruption, whereas CLZ, RIS and QUE induced an early onset but shorter duration disruption. In addition, only the atypical antipsychotics showed some inhibitory effects on nursing behavior, possibly due to sedative side-effects shared by all atypical antipsychotics. The current generation of atypical antipsychotics shows a disruptive influence on maternal behavior similar to that of the typical antipsychotics. This effect may be intrinsic to antipsychotic activity or may be reflective of a side-effect. Since the latter is more likely, this may be an effect to avoid in the design of future antipsychotics.
Med J Aust. 2004 Aug 16;181(4):207-10. : Major advances in bipolar disorder.
Mitchell PB, Malhi GS, Ball JR.
School of Psychiatry, University of New South Wales, Prince of Wales Hospital, Randwick, NSW 2031, Australia.
phil.mitchell@unsw.edu.au
There have been major advances in clinical understanding and treatment of bipolar disorder over the past decade. Randomised controlled trials of pharmacological treatments and psychological interventions have shown that there are effective short-term and long-term treatments for the disorder. Despite advances in treatment, diagnosis is often delayed or mistaken, and many people who could benefit are not using the treatments available. Functional and symptomatic recovery from episodes of bipolar disorder is frequently less complete than previously considered, and disability is often profound. Although manic episodes are the distinguishing feature of bipolar disorder, it appears that depression is the predominant mood disturbance and that much of the functional impairment associated with bipolar disorder results from this. Comorbidity with anxiety disorders or substance misuse is common. Advances in genetics, brain imaging and basic pharmacology are starting to provide understanding of the complex causative processes.
Biol Psychiatry. 2004 Nov 15;56(10):771-7. : New medication strategies for comorbid substance use and bipolar affective disorders.
Kosten TR, Kosten TA.
Department of Psychiatry, Yale University School of Medicine, Veterans Affairs Connecticut Healthcare System, West Haven, Connecticut, USA. Comorbidity of substance abuse disorders (SUD) with bipolar disorders (BPD) is a serious treatment problem. Childhood BPD can be further complicated by comorbidity with attention-deficit/hyperactivity disorder (ADHD) and later SUD during adolescence. The aim of this article is to review the literature on pharmacotherapies for these patients. Developing the ideal pharmacotherapy for BPD and SUD can be informed by the role of gamma-aminobutyric acid (GABA) in the neurobiology of SUD. This ideal pharmacotherapy would have several key characteristics. These characteristics include treating the BPD, relieving withdrawal symptoms, and preventing relapse to SUD. The ideal medication should have low abuse liability, require infrequent dosing, be well tolerated, and have few side effects. A medication approaching this ideal is the GABA enhancer valproate. Adding atypical antipsychotic agents might not improve valproate's efficacy, but combining GABA medications with selective serotonin reuptake inhibitors holds promise for SUD with depression. Pemoline might be the best option for minimizing the risk of SUD complicating comorbid ADHD with BPD.
CNS Spectr. 2004 Nov;9(11):823-32. : Therapy of Treatment Resistant Depression: Focus on the Management of TRD with Atypical Antipsychotics.
Klein N, Sacher J, Wallner H, Tauscher J, Kasper S.
Department of General Psychiatry, Medical University of Vienna, Vienna, Austria.
Treatment-resistant depression (TRD) represents a significant challenge for physicians. About one third of patients with major depressive disorder fail to experience sufficient symptom improvement despite adequate treatment. Despite this high occurrence of TRD there was no general consensus on diagnosis criteria for TRD until 1997 when researchers proposed a model of defining and staging TRD. In 1999, others defined operational criteria for the definition of TRD. Treatment of TRD is commonly separated into pharmacologic and nonpharmacologic methods. This review gives a short overview of these two methods. The nonpharmacologic methods include psychotherapy, electroconvulsive therapy, and vagus nerve stimulation. Pharmacologic methods include switching to another antidepressant monotherapy, and augmentation or combination with two or more antidepressants or other agents. This review especially focuses on the augmentation of the antidepressant therapy with atypical antipsychotics
CNS Spectr. 2004 Oct;9(10):740-52. : Treatment-resistant posttraumatic stress disorder: strategies for intervention.
Hamner MB, Robert S, Frueh BC.
Department of Psychiatry and Behavioral Sciences, Medical University of South Carolina, Charleston, USA.
hamnermb@musc.edu
The mainstay of treatment for chronic posttraumatic stress disorder (PTSD) is a combination of psychotherapy and medication treatments. The first-line medications for PTSD are antidepressants, with two selective serotonin reuptake inhibitors (sertraline and paroxetine) currently Food and Drug Administration-indicated for PTSD. However, many patients do not have an adequate response to antidepressants, therefore, combinations with other antidepressants or with other classes of psychotropic medication are often utilized to enhance the therapeutic response. Other agents that have been used include mood stabilizers, anti-adrenergics, anxiolytics, and atypical antipsychotics. The heterogeneity of symptom clusters in PTSD as well as the complex psychiatric comorbidities (eg, with depression or substance abuse) further support the notion that combinations of medications may be needed. To date, there is a paucity of data to support specific strategies for augmenting antidepressants in PTSD. This review will address representative existing studies and discuss several potential pharmacologic strategies for patients suffering from treatment-refractory PTSD.
Brain Cogn. 2004 Aug;55(3):463-5. : Cognitive function and depression in symptom resolution in schizophrenia patients treated with an atypical antipsychotic.
Stip E, Mancini-Marie A.
Fernand Seguin Research Center, Louis-H Lafontaine Hospital, University of Montreal, Montreal, Que., Canada.
emmanuel.stip@umontreal.ca
OBJECTIVE: To investigate which cognitive and affective features contribute most to responder/non-responder group separation during a switching trial with atypical antipsychotic. DESIGN: A prospective open trial with an atypical antipsychotic (olanzapine). PATIENTS: One hundred and thirty-four patients meeting diagnostic criteria for schizophrenia, schizophreniform or schizoaffective disorder began an 8-week open-label olanzapine treatment at a dose of 5 mg/day which was increased to 10 mg/day after one week. INTERVENTIONS: Olanzapine during 8 weeks. Patients were considered as responders if their BPRS score decreased of at least 20% (n = 96) and non-responders if it did not (n = 38). Neuropsychological assessments were carried out at baseline, at four and at eight weeks. RESULTS: Neurocognitive measures were analyzed for discriminate factors between responder and non-responder groups. A regression analysis was applied to explain the effects of depression on each cognitive variable. Depression was found to be a weak discriminant factor, however this finding could not firmly establish that depression is a potential factor in explaining deficits and improvements in cognition.
: Expert Opin Pharmacother. 2004 Jul;5(7):1613-9. : Olanzapine in bipolar disorder.
Vieta E.
University of Barcelona, Bipolar Disorders Program, Hospital Clinic, Villarroel 170, Rossello 140, 08036 Barcelona, Spain.
evieta@clinic.ub.es
Olanzapine is currently marketed not only for the treatment of schizophrenia, but also for the treatment of acute mania and the prevention of relapse in patients successfully treated with this drug for a manic episode. A large body of good clinical trials supports these indications. In the mania trials, olanzapine was more efficacious than placebo, equal or more efficacious than valproate and more efficacious than lithium or valproate monotherapy when used in combination with either drug. A trial that compared olanzapine with haloperidol failed to show superiority of the atypical versus the conventional. Olanzapine showed a modest but statistically significant effect in the treatment of bipolar depression; this modest effect was substantially enhanced in combination with fluoxetine. The long-term trials showed that olanzapine was better than placebo in the prevention of manic and depressive relapse and not inferior to lithium or valproate. The combination of olanzapine with lithium or valproate was also more efficacious than lithium or valproate alone in the prevention of manic relapse in patients partially non-responding to monotherapy with lithium or valproate. All these trials suggest that olanzapine may be a valuable drug in the short- and long-term treatment of bipolar I disorder. However, there are some concerns about the safety and tolerability of olanzapine in this population, as far as weight gain and metabolic syndrome are concerned, which may be addressed in future pharmacovigilance studies.
: J Clin Psychiatry. 2004 Jul;65(7):975-81. : The effectiveness of olanzapine, risperidone, quetiapine, and ziprasidone as augmentation agents in treatment-resistant major depressive disorder.
Barbee JG, Conrad EJ, Jamhour NJ.
Department of Psychiatry, Louisiana State University Health Sciences Center, New Orleans 70112, USA.
jbarbe@lsuhsc.edu
BACKGROUND: Many questions remain regarding the use of atypical neuroleptics as antidepressant augmentation agents. To date, there have been no reports in the literature regarding the effectiveness of these drugs when trials of one or more of them have failed previously as antidepressant augmentation. METHOD: This retrospective chart review was conducted to determine the effectiveness of olanzapine, risperidone, quetiapine, and ziprasidone when given in a fee-for-service setting as anti-depressant augmentation agents to patients with treatment-resistant, nonpsychotic major depressive disorder (DSM-IV). Prospective (Global Assessment of Functioning [GAF]) along with retrospective (Clinical Global Impressions-Improvement [CGI-I] and -Severity of Illness scales) ratings were completed for each patient. Analyses were conducted in an attempt to identify factors that appeared to correlate with response, including order of administration and Thase-Rush staging of treatment resistance. RESULTS: In this study of 76 medication trials in 49 patients, the overall response rate based on the CGI-I ratings was 65% (32/49). Individual rates of response were 57% (21/37) for olanzapine, 50% (7/14) for risperidone, 33% (6/18) for quetiapine, and 10% (1/10) for ziprasidone. None of the differences between neuroleptics in rates of response were significant. The difference between baseline and final GAF scores was statistically significant only in the olanzapine (p <.001) and risperidone (p =.047) groups. Rates of discontinuation did not vary significantly between agents, though trends were present. Crossover trials from one atypical neuroleptic to another in the event of nonresponse appeared to be effective. CONCLUSIONS: Although limited by its design, this study suggests atypical neuroleptic augmentation of antidepressants may be a viable option in treatment-resistant major depressive disorder.
: J Psychopharmacol. 2004 Jun;18(2):281-4. : Does quetiapine have mood altering properties?
Mishra A, Moore PB, Hobbs R.
Mental Health Unit, Leazes Wing, Royal Victoria Infirmary, Newcastle Upon Tyne, UK.
achdoc@aol.com
We present a series of three cases who developed manic symptoms on introduction of quetiapine to their medication regime. All were male, with long-standing psychotic illnesses (schizophrenia/schizoaffective disorder), relatively well maintained on medication until their deterioration which prompted a review of their medication. The dose range of prescribed quetiapine was 300-800 mg daily. Two patients had previously received antidepressants without displaying manic symptoms. The mania subsided on withdrawal of quetiapine in two patients. The third patient continued on quetiapine but with the addition of zuclopenthixol depot. Sodium valproate was prescribed to the other two patients, and quetiapine was discontinued. These cases indicate that a side-effect of quetiapine may be mood elevation. An ability to elevate mood while controlling psychoses would be helpful in the treatment of post-psychotic and bipolar depression. Its clinical importance in the control of manic episodes, for which atypical antipsychotics are used increasingly, is uncertain
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