If you have GAD, you don't stop worrying and fear the
worst. You can't relax. More women than men have it. It usually starts as a child or teenager. They may have headaches or trouble falling asleep. About four million Americans suffer from generalized anxiety disorder. U.S. Food and Drug Administration (FDA) has approved Lexapro™ (escitalopram oxalate), a selective serotonin reuptake inhibitor (SSRI), for the treatment of generalized anxiety disorder (GAD) "EFFEXOR® XR (venlafaxine HCl), a serotonin-norepinephrine reuptake inhibitor (SNRI) , first antidepressant approved for the treatment of GAD, is the only antidepressant indicated for the short- and long-term treatment of patients of generalized anxiety disorder FDA approved Paxil® (paroxetine HCl) for the treatment of generalized anxiety disorder (GAD). Buspirone is a 5-HT1A receptor partial agonist with FDA approval for GAD.
. Some feel that the symptoms of GAD and bipolar II overlap.
An excellent overview on generalized anxiety disorder and drug treatment "The anxiety and worry are associated with three (or more) of the following six symptoms (with at least some
symptoms present for more days than not for the past six months). NOTE: Only one item is required in
children.
Restlessness or feeling keyed up or on edge
Being easily fatigued
Difficulty concentrating or mind going blank
Irritability
Muscle tension
Sleep disturbance (difficulty falling or staying asleep, or restless unsatisfying sleep "It is more
prevalent in women than in men,1 with the median age of
onset occurring during the early 20s.13 The onset of symptoms is usually gradual, although GAD can be precipitated
by stressful life events. The condition tends to be chronic with periods of exacerbation and remission.13
"
: Hum Psychopharmacol. 2004 Oct;19(7):457-65. :
The acute effects of L-theanine in comparison with alprazolam on anticipatory anxiety in humans.
Lu K, Gray MA, Oliver C, Liley DT, Harrison BJ, Bartholomeusz CF, Phan KL, Nathan PJ.
Neuropsychopharmacology Laboratory, Brain Sciences Institute, Swinburne, University of Technology, Victoria, Australia.
L-Theanine (delta-glutamylethylamide) is one of the predominant amino acids ordinarily found in green tea, and historically has been used as a relaxing agent. The current study examined the acute effects of L-theanine in comparison with a standard benzodiazepine anxiolytic, alprazolam and placebo on behavioural measures of anxiety in healthy human subjects using the model of anticipatory anxiety (AA). Sixteen healthy volunteers received alprazolam (1 mg), L-theanine (200 mg) or placebo in a double-blind placebo-controlled repeated measures design. The acute effects of alprazolam and L-theanine were assessed under a relaxed and experimentally induced anxiety condition. Subjective self-reports of anxiety including BAI, VAMS, STAI state anxiety, were obtained during both task conditions at pre- and post-drug administrations. The results showed some evidence for relaxing effects of L-theanine during the baseline condition on the tranquil-troubled subscale of the VAMS. Alprazolam did not exert any anxiolytic effects in comparison with the placebo on any of the measures during the relaxed state. Neither L-theanine nor alprazalam had any significant anxiolytic effects during the experimentally induced anxiety state. The findings suggest that while L-theanine may have some relaxing effects under resting conditions, neither L-theanine not alprazolam demonstrate any acute anxiolytic effects under conditions of increased anxiety in the AA model. 2004 John Wiley & Sons, Ltd.
Behav Res Ther. 2004 Aug;42(8):881-92. :
Interpretive cues and ambiguity in generalized anxiety disorder.
Hazlett-Stevens H, Borkovec TD .
Department of Psychology/298, University of Nevada, Reno, NV 89557, USA. The current study investigated whether generalized anxiety disorder (GAD) individuals rely on antecedent information to interpret ambiguity and whether reliance on such preceding cues persists in the absence of potential threat. Twenty-six GAD and 23 nonanxious control college students performed a lexical decision task, using homographs (i.e. words with multiple meanings) as ambiguous primes. In half the trials, a homograph prime that possessed both threat-related, as well as neutral meanings was followed by a target word related to one of these two meanings. In addition, each ambiguous prime was immediately preceded by a series of four antecedent words that were either: (a) associated with the threatening meaning of the prime; (b) associated with the neutral meaning of the prime; or (c) unrelated to either meaning of the homograph, as well as the target. Homographs for which both meanings were neutral in valence comprised the other half of the trials. Effect size statistics suggest that GAD participants utilized the antecedent words to interpret the homograph primes with threat-related meanings, unlike their nonanxious counterparts ( [Formula: see text] ). When both meanings of the homograph prime were neutral in valence, the GAD group appeared deficient in the use of preceding information to interpret the ambiguous prime.
Am J Psychiatry. 2004 Jun;161(6):1119-21. :
Dorsolateral prefrontal cortical pathology in generalized anxiety disorder: a proton magnetic resonance spectroscopic imaging study.
Mathew SJ, Mao X, Coplan JD, Smith EL, Sackeim HA, Gorman JM, Shungu DC.
Department of Biological Psychiatry, New york State Psychiatric Institute, Columbia Unversity, New York, NY 10032, USA. sm524@columbia.edu
OBJECTIVE: Few neuroimaging studies of generalized anxiety disorder have been conducted. The present study used proton magnetic resonance spectroscopy to assess concentrations of N-acetylaspartate, often considered a marker of neuronal viability, in generalized anxiety disorder patients. METHOD: N-Acetylaspartate/creatine resonance ratios were measured in the left and right dorsolateral prefrontal cortex and hippocampus of 15 medication-free generalized anxiety disorder patients and 15 age- and sex-matched healthy volunteers. RESULTS: Generalized anxiety disorder patients had a 16.5% higher N-acetylaspartate/creatine ratio in the right dorsolateral prefrontal cortex compared with healthy participants; 13 of 15 matched patient-comparison subject pairs displayed a difference in this direction. In addition, generalized anxiety disorder patients reporting childhood abuse had lower N-acetylaspartate/creatine ratios in the right dorsolateral prefrontal cortex than did nonabused patients. Metabolite differences were not detected in other regions. CONCLUSIONS: Generalized anxiety disorder is associated with asymmetric increases in the N-acetylaspartate/creatine ratio, a suggested marker of neuronal viability, in the prefrontal cortex. The findings also support prior research linking childhood abuse to reduced neuronal viability.
J Affect Disord. 2004 Jun;80(2-3):163-71. :
Comorbidity of generalized social anxiety disorder and depression in a pediatric primary care sample.
Chavira DA, Stein MB, Bailey K, Stein MT.
Department of Psychiatry, University of California San Diego, 8950 Villa La Jolla Drive, Suite 2243, La Jolla, CA 92037, USA.
BACKGROUND: Comorbidity between adult social anxiety disorder and major depression is extensive. Considerably less information about this relationship is available among youth. METHODS: A randomly selected (from enrollees in a pediatric primary care clinic) sample of 190 families with children between the ages of 8 and 17 responded by mail to questionnaires assessing social anxiety, depression, and social functioning. Parents also completed a semi-structured telephone diagnostic interview about their child. RESULTS: The generalized type of social anxiety disorder was highly comorbid with major depression, generalized anxiety disorder, specific phobias, and ADHD, while little comorbidity was present for the nongeneralized subtype of social anxiety disorder. Logistic regression analyses indicated that generalized social anxiety disorder was the only anxiety disorder associated with an increased likelihood of major depression (OR=5.1). In all cases, social anxiety disorder had a significantly earlier age of onset than major depression. LIMITATIONS: This study relies on cross-sectional data and diagnoses are based on parent reporting of child behavior. CONCLUSIONS: Generalized social anxiety disorder is strongly associated with depressive illness in youth. Screening and treatment approaches that consider both social anxiety and depressive symptoms are necessary. Early intervention to treat social anxiety disorder may prevent later depressive disorders. Copyright 2003 Elsevier B.V.J Am Acad Child Adolesc Psychiatry. 2004 Jun;43(6):752-60. :
Generalized anxiety disorder in referred children and adolescents.
Masi G, Millepiedi S, Mucci M, Poli P, Bertini N, Milantoni L.
IRCCS Stella Maris, Scientific Institute of Child Neurology and Psychiatry, Calambrone, Pisa, Italy. gabrielle.masi@inpe.unipi.it
OBJECTIVE: There are insufficient data on generalized anxiety disorder in children and adolescents. Symptoms and comorbidity of generalized anxiety disorder are described as a function of age, gender, and comorbidity in a consecutive series of referred children and adolescents. METHOD: One hundred fifty-seven outpatients (97 males and 60 females, 50 children and 107 adolescents, age range 7-18 years, mean age 13.4 +/- 2.7 years) were diagnosed as having generalized anxiety disorder, using historical information and a structured clinical interview (Diagnostic Interview for Children and Adolescents-Revised) according to the DSM-IV. RESULTS: Feelings of tension, apprehensive expectations, negative self-image, need for reassurance, irritability, and physical complaints were reported in more than 75% of the participants. Differences in symptomatology according to age and gender were nonsignificant. Depressive disorder was the most frequent comorbidity, being present in 56% of the patients. Comorbid anxiety disorders were present in about 75% of the patients, and 21% showed externalizing disorders. Subjects with comorbid depression had less anxiety comorbidity, subjects with comorbid separation anxiety disorder had higher rates of panic disorder, and subjects with comorbid externalizing disorders had higher rates of bipolar disorder. CONCLUSIONS: Referred children and adolescents with generalized anxiety disorder are heavily symptomatic and have frequent comorbidity. A more precise definition of the clinical picture may help early diagnosis and prevention of superimposed mental disorders.Clin Psychol Rev. 2004 May;24(2):149-69. :
Psychosocial treatment of late-life generalized anxiety disorder: current status and future directions.
Mohlman J.
Department of Psychology, Syracuse University, 430 Huntington Hall, Syracuse, NY 13244, USA. jmohlman@syr.edu
Although generalized anxiety disorder (GAD) was once an understudied illness, there has been an increase in research on the disorder over the past several years. A subset of studies has focused on the psychosocial treatment of late-life GAD. It was initially expected that cognitive behavior therapy (CBT) would prove to be the most effective treatment for GAD in the elderly. Although group format CBT has outperformed no-treatment control conditions in some studies, the existing body of work does not clearly indicate the superiority of CBT over alternative interventions [e.g., supportive therapy (ST)]. Trials of individual format CBT have tested augmented or otherwise nonstandard versions of the therapy. Therefore, it may not be appropriate to assume a smooth transfer of CBT benefits across age groups in the treatment of GAD. This review summarizes and discusses the current state of psychosocial interventions for late-life GAD, including group and individual format CBT, limitations of existing research, and suggestions for future directions.
Eur Psychiatry. 2004 Apr;19(2):96-101. :
Long term therapy of generalized anxiety disorder.
Rouillon F.
Psychiatry Department, Hospital Albert Chenevier, 40, rue de Mesly, 94010 Creteil, France.
Generalized anxiety disorder (GAD) is a common (lifetime prevalence: 5.1%), recurrent condition, which often heralds other psychiatric disorders, notably depression. As by definition it is a disorder progressing over months, treatment should be designed on a long term basis. And yet, few studies have been conducted beyond the classical 6-8 weeks characterizing the acute treatment phase. This is especially true of anxiolytics, but also of antidepressants, with the exception of paroxetine and venlafaxine, which are the only drugs approved in this indication in Western countries. The efficacy of psychotherapy, notably relaxation and cognitive-behavioral therapy, is established in the treatment of GAD, but its preferred indications and possible combination with antidepressants are still to be specified. Long term, not to say very long term studies of GAD, as well as depression, will still be required in the future to improve its management and specify therapeutic modalities (combination treatment, optimal duration, continuous or intermittent therapy, choice of psychotherapeutic techniques or agents, em leader ). Early and adequately prolonged treatment should not only result in more numerous remission periods, but also in decreased frequency of co-morbidities whether depressive, addictive, or of another nature, and should also reduce the social impact of GAD.J Affect Disord. 2004 Apr;79(1-3):161-6. :
Well-being and life satisfaction in generalized anxiety disorder: comparison to major depressive disorder in a community sample.
Stein MB, Heimberg RG.
Anxiety and Traumatic Stress Disorders Program Department of Psychiatry (0985), University of California San Diego, La Jolla, CA 92093-0985, USA. mstein@ucsd.edu
BACKGROUND: In most settings, generalized anxiety disorder (GAD) is highly comorbid with major depressive disorder (MDD). This raises uncertainty about the clinical relevance of GAD as a distinct diagnostic entity. The demonstration of functional impairment attached to GAD, independent of that attributable to MDD, would support the importance of GAD as a separate diagnostic category. METHODS: The Ontario Health Survey Mental Health Supplement, a survey of more than 8000 residents aged 15-64 of the Canadian province of Ontario, used the University of Michigan Composite International Interview Schedule (also used in the US National Comorbidity Survey) to assign DSM-III-R diagnoses. Several indicators of disability and quality of life were included. Our analytic strategy was to compare these indices in persons with and without GAD, stratified by MDD comorbidity, and adjusting for the effects of relevant sociodemographic factors (e.g., social class, age, gender) and dysthymia. Odds ratios (ORs) are reported; SUDAAN was used to adjust for the sampling framework. RESULTS: GAD was highly comorbid with MDD on both a lifetime and past-year basis. Both past-year and lifetime MDD and GAD were associated with an increased likelihood of low overall perceived well-being. Both lifetime MDD and GAD were associated with dissatisfaction in one's main activity and with family relationships. LIMITATIONS: Other comorbid Axis I or II conditions might be confounders with impairment; a lower rate of GAD than in some prior surveys bears consideration. CONCLUSIONS: These observations confirm that GAD is associated with an increased likelihood of poor global well-being and life satisfaction, beyond that associated with MDD. Given the chronicity of GAD relative to the more often episodic course of MDD, the long-term functional benefits of treating GAD may be substantial.Fluvoxamine-Luvox J Clin Psychopharmacol. 2004 Apr;24(2):118-25. :
Fluvoxamine-controlled release formulation for the treatment of generalized social anxiety disorder.
Davidson J, Yaryura-Tobias J, DuPont R, Stallings L, Barbato LM, van der Hoop RG, Li D.
Department of Psychiatry, Duke University Medical Center, Trent Drive, 4th Floor, Room 4082B, Durham, NC 27710, USA. jonathan.davidson@duke.edu BACKGROUND: Generalized social anxiety disorder is a highly prevalent anxiety disorder with deleterious effects on social and family relationships, as well as work performance. We report the results of a multicenter, randomized, placebo-controlled trial comparing the efficacy, safety, and tolerability of fluvoxamine controlled release (CR) to placebo in patients with generalized social anxiety disorder. METHODS: A total of 279 adult patients meeting all inclusion/exclusion criteria was recruited at 23 United States sites and randomly assigned to receive either fluvoxamine CR (100-300 mg/d) or placebo for 12 weeks. The dose could be increased, based on efficacy and tolerability, in increments of 50 mg/d at weekly intervals. The dosage remained constant during weeks 6 to 12. RESULTS: Treatment with fluvoxamine CR resulted in statistically and clinically significant improvements in symptoms associated with generalized social anxiety disorder as early as week 4 on the Liebowitz Social Anxiety Scale and the Clinical Global Impression Scale Global Improvement, and at week 6 on the Sheehan Disability Scale, Clinical Global Impression Scale Severity of Illness and the Patient Global Impression of Improvement Scale. The most frequent adverse events reported by patients on fluvoxamine CR were headache, nausea, somnolence, and insomnia. No weight gain was observed for either treatment group, and at end point, there were no differences between treatments on overall sexual function, as measured by the Arizona Sexual Experience Scale. CONCLUSIONS: Both physician and patient-rated scales indicate that fluvoxamine CR is effective and safe for the treatment of generalized social anxiety disorder.J Clin Psychopharmacol. 2004 Feb;24(1):49-55. :
A double-blind placebo-controlled study of controlled release fluvoxamine for the treatment of generalized social anxiety disorder.
Westenberg HG, Stein DJ, Yang H, Li D, Barbato LM.
Department of Biological Psychiatry, University Hospital Utrecht, The Netherlands. h.g.m.westenberg@azu.nl This was a randomized double-blind placebo-controlled multicenter study to assess the efficacy, safety, and tolerability of fluvoxamine in a controlled release (CR) formulation for treatment of generalized social anxiety disorder (GSAD). A total of 300 subjects with GSAD were randomly assigned to receive either fluvoxamine CR (N = 149) or placebo (N = 151) for 12 weeks. Mean changes from baseline to end point in Liebowitz Social Anxiety Scale (LSAS), Clinical Global Impression Severity of Illness Scale (CGI-S), Sheehan Disability Scale (SDS), as well as the mean end point scores in Clinical Global Impression Improvement Scale (CGI-I) and Patient Global Impression of Improvement Scale (PGI) were compared between the fluvoxamine CR and placebo treatment groups. Arizona Sexual Experience Scale (ASEX), adverse event, and other safety parameters were also assessed. The results demonstrated that fluvoxamine CR was significantly superior to placebo in decreasing LSAS total score (primary measure) starting at week 4. At end point, there was a mean change from baseline of -36.1 +/- 2.7 (37% reduction) in the LSAS total score in the fluvoxamine CR group compared with -27.3 +/- 2.4 (28% reduction) in the placebo group (P = 0.020 for mean change). Fluvoxamine CR was also significantly superior to placebo in SDS, CGI-S, CGI-I at end point (secondary measures). When compared with placebo, fluvoxamine CR did not cause any significant weight gain or clinically significant sexual dysfunction as measured by ASEX. In summary, fluvoxamine CR is an efficacious, safe, and well-tolerated treatment of generalized social anxiety disorder.
J Anxiety Disord. 2004;18(4):561-71. :
Insomnia and generalized anxiety disorder:; Effects of cognitive behavior therapy for gad on insomnia symptoms.
Belanger L, Morin CM, Langlois F, Ladouceur R.
Ecole de Psychologie, Universite Laval, Laval, Que., Canada G1K 7P4. Although clinical practice suggests that sleep complaints are frequent among patients with generalized anxiety disorder (GAD), frequency, severity, types of insomnia complaints, and relationship to GAD diagnosis severity in patients diagnosed using Diagnostic and Statistical Manual of Mental Disorders (DSM-IV) criteria are not well documented. Clinical data about the impact on insomnia symptoms of treating GAD worries are also lacking. The present study examined these aspects in 44 GAD patients who participated in a treatment study specifically addressing excessive worries through CBT interventions. All patients were assessed using a structured clinical interview and the Anxiety Disorder Interview Schedule-IV (ADIS-IV). They also completed anxiety and insomnia inventories, including the Insomnia Severity Index (ISI), a self-report measure which assesses insomnia type, severity and interference with daily life. Among this sample, 47.7% reported difficulties initiating sleep, 63.6% reported difficulties maintaining sleep, and 56.8% complained of waking too early in the morning. The majority of these patients (86.5%) reported never having experienced insomnia without having excessive worries. However, insomnia severity and GAD severity were not correlated. In this sample, patients with severe GAD did not necessarily report more severe insomnia symptoms. Regarding treatment impact on insomnia complaints, ISI post-treatment scores were significantly lower after treatment. Mean post-treatment scores almost reached ISI's "absence of clinical insomnia" category. Results indicate that this CBT package for GAD does have a significant impact on sleep quality even if sleep disturbances were not specifically addressed during treatment.
J Anxiety Disord. 2004;18(3):275-90. :
Distinguishing generalized anxiety disorder, panic disorder, and mixed anxiety states in older treatment-seeking adults.
Mohlman J, de Jesus M, Gorenstein EE, Kleber M, Gorman JM, Papp LA.
Department of Psychiatry, New York State Psychiatric Institute, Columbia University, Box 14, 1051 Riverside Drive, New York, NY 10032, USA. jmohlman@psych.syr.edu
Eighty treatment-seeking adults age 60 or over with panic disorder, generalized anxiety disorder, and mixed anxiety states (generalized anxiety with panic attacks, panic disorder with secondary generalized anxiety) completed a clinical assessment and battery of self report measures. Several hypotheses were tested from the domains of distinguishing symptoms, associated features, and rates of comorbidity with other disorders. Greater between- than within-group variance was found on a subset of measures suggesting that the distinction between GAD and PD is generally valid in the older adult population. Higher scores on measures of sympathetic arousal, agoraphobic avoidance, and rates of comorbid somatization disorder and alcohol dependence distinguished those with PD from those with GAD. Higher scores on measures of depression and hostility, but not trait anxiety or worry, distinguished the GAD group. Results indicate that distinguishing features of GAD and PD in older treatment-seeking adults may be fewer and slightly different from those of younger adults.
J Clin Psychiatry. 2004;65 Suppl 5:29-33. :
Use of benzodiazepines in social anxiety disorder, generalized anxiety disorder, and posttraumatic stress disorder.
Davidson JR.
Department of Psychiatry and Behavioral Sciences, Duke University Medical Center South, Durham, NC 27710, USA. jonathan. davidson@duke.edu
Benzodiazepines are advantageous treatments for anxiety disorders because they work quickly. However, benzodiazepines can vary in terms of efficacy across anxiety disorders. Benzodiazepines have been found to be a superior treatment in social anxiety disorder. While benzodiazepines are effective in the treatment of generalized anxiety disorder, other treatments such as selective serotonin reuptake inhibitors may be more effective. Also, research indicates that benzodiazepines may not be effective in the treatment of posttraumatic stress disorder. Therefore, physicians need to consider the type of anxiety disorder before prescribing a benzodiazepine as a treatment.
Cogn Behav Neurol. 2003 Dec;16(4):225-33. :
Correlates of generalized anxiety and panic attacks in dystonia and Parkinson disease.
Lauterbach EC, Freeman A, Vogel RL.
Departments of Psychiatry and Behavioral Sciences, Internal Medicine (Neurology), and Radiology and Family Medicine and Community Medicine of Mercer University School of Medicine, Macon, Georgia 31201, USA. lauterbach_e@mercer.edu
OBJECTIVE:To determine prevalences of generalized anxiety, generalized anxiety disorder, panic attacks, and panic disorder in primary dystonia (n = 28) and Parkinson disease (n = 28) and to explore their clinical correlates. BACKGROUND: We previously identified increases in Diagnostic and Statistical Manual of Mental Disorders, third edition generalized anxiety in dystonia and panic attacks in Parkinson disease. METHOD: Structured Clinical Interview (SCID) ascertainment of Diagnostic and Statistical Manual of Mental Disorders, third edition, revised, disorders. RESULTS: Generalized anxiety disorder was more common in dystonia while panic disorder was more common in Parkinson disease (P = 0.0018). Generalized anxiety developed more commonly after dystonia onset (i.e., secondary generalized anxiety) while panic attacks developed more commonly after Parkinson disease onset (P = 0.0132). Specific life prevalences were: generalized anxiety disorder, 7 subjects (25.0%) in dystonia versus 0 subjects (0.0%) in Parkinson disease; generalized anxiety, 11 (39.3%) versus 0 (0.0%); panic disorder, 2 (7.1%) versus 7 (25.0%); and panic attacks, 2 (7.1%) versus 9 (32.1%). Exploratory analysis in Parkinson disease indicated a relationship of panic disorder (P = 0.027) and secondary panic attacks (P = 0.0009) to motor block frequency. There were nonsignificant trends toward associations of secondary generalized anxiety with lower Mini Mental Status Examination scores (P = 0.058), and of secondary panic attacks with presence of a depressive disorder (P = 0.077). Depressive comorbidity rates are also presented. CONCLUSIONS: These findings suggest relations of generalized anxiety with reduced pallidal inhibition of thalamofrontotemporal projections, and panic attacks with locus coeruleus dysfunction.
J Clin Psychiatry. 2004 Feb;65(2):244-8. :
Double-blind, placebo-controlled assessment of combined clonazepam with paroxetine compared with paroxetine monotherapy for generalized social anxiety disorder.
Seedat S, Stein MB.
Anxiety and Traumatic Stress Disorders Program, Psychiatry Service, VA San Diego Healthcare System, San Diego, CA, USA. sseedat@sun.ac.za
BACKGROUND: Generalized social anxiety disorder (GSAD) is a pervasive form of social anxiety that affects approximately 5% of persons in the community. Among evidence-based pharmacologic treatments for the disorder, selective serotonin reuptake inhibitors (SSRIs) have become widely used and are known to be efficacious. Monotherapy with the benzodiazepine clonazepam is also efficacious for GSAD, but the adjunctive use of clonazepam with an SSRI to potentially improve outcomes has not been studied to date. METHOD: Twenty-eight patients (22 men and 6 women) with DSM-IV-defined GSAD were randomly assigned to receive double-blind clonazepam (or placebo), 1.0 to 2.0 mg/day (divided b.i.d.) along with open-label paroxetine, 20 to 40 mg/day, for 10 weeks. A 2-week taper of double-blind medication was followed by an additional 8 weeks of open-label paroxetine treatment (during which the dose of paroxetine could be increased to a maximum of 50 mg/day). Twenty-three patients (82%) met DSM-IV criteria for avoidant personality disorder. The patients' mean +/- SD age was 31.2 +/- 7.7 years, and their mean duration of illness was 12.1 +/- 5.8 years. Data were gathered from August 2001 to April 2002. RESULTS: Nineteen (68%) of 28 patients completed treatment. At the end of the 10-week double-blind treatment, there was a trend (p <.06) favoring the paroxetine/clonazepam group, who had a 79% response rate (Clinical Global Impressions-Global Improvement scale [CGI-I] score of 1 or 2) compared with a 43% response rate for the paroxetine/placebo group. However, no significant differences on other outcome measures were noted between the 2 groups in an intent-to-treat analysis, in terms of either very early (2-4 weeks) or not as early (5-10 weeks) responses during treatment. Dropout rates due to adverse events were rare (1 patient in each group), indicating that the paroxetine/clonazepam combination was well tolerated. CONCLUSION: Coadministration of clonazepam with an SSRI, in contrast to findings in panic disorder, did not lead to more rapid resolution of symptoms in GSAD. On the other hand, there is some evidence that the clonazepam-added group had superior global outcomes (e.g., as measured on the CGI-I), although power to detect such differences in this study was small. These observations suggest that a role for adjunctive benzodiazepines in patients with GSAD (e.g., for augmenting SSRI partial response or nonresponse) is deserving of further controlled investigation
Panminerva Med 2002 Dec;44(4):283-6
:
The treatment of generalised anxiety disorder. A systematic
review.
Gale CK.
South Auckland Clinical School and Division of Psychiatry, Faculty of Medicine and
Health Sciences, University of Auckland, Auckland, New Zealand. We have reviewed the treatment of generalised anxiety disorder (GAD). Previous
systematic reviews, clinical guidelines, and controlled trials were critically
appraised, and described. Cognitive therapy, anxiety management therapy, certain
antidepressants (paroxetine, imipramine, trazodone, opipramol), benzodiazeines
and buspirone are effective treatments for GAD. The application of these
findings in the clinical situation was discussed.
Lumiscope 1247 Electronic Pill Timer
Am J Psychiatry 2003 Mar;160(3):504-12
:
Generalized Anxiety Disorder in Patients With Major Depression:
Is DSM-IV's Hierarchy Correct?
Zimmerman M, Chelminski I. OBJECTIVE: DSM-III imposed a hierarchical relationship in the diagnosis of
anxiety disorders in depressed patients, stipulating that anxiety disorders could not
be diagnosed if their occurrence was limited to the course of a mood disorder. In
the subsequent versions of the DSM this hierarchy was eliminated for all anxiety
disorders except generalized anxiety disorder. The authors examined the validity of
this remaining hierarchical relationship between mood and anxiety disorders.
METHOD: Psychiatric outpatients with major depressive disorder (N=332) were
evaluated with a semistructured diagnostic interview and completed
paper-and-pencil questionnaires on presentation for treatment. To study the validity
of the DSM-IV hierarchical relationship between generalized anxiety disorder and
mood disorders, the authors made a diagnosis of modified generalized anxiety
disorder for patients with major depressive disorder who met all the criteria for
generalized anxiety disorder except for the exclusion criterion. The analyses
compared the characteristics of three nonoverlapping groups of patients with
DSM-IV major depressive disorder: 1) those with coexisting DSM-IV generalized
anxiety disorder, 2) those with coexisting modified generalized anxiety disorder,
and 3) those with neither DSM-IV nor modified generalized anxiety disorder.
RESULTS: Compared to the depressed patients without generalized anxiety
disorder, the depressed patients with DSM-IV and modified generalized anxiety
disorder had higher levels of suicidal ideation; poorer social functioning; a greater
frequency of other anxiety disorders, eating disorders, and somatoform disorders;
higher scores on most subscales of a multidimensional self-report measure of
DSM-IV axis I disorders; a greater level of pathological worry; and a higher morbid
risk for generalized anxiety disorder in first-degree family members. The two
generalized anxiety disorder groups did not differ from each other.
CONCLUSIONS: The findings question the validity of the DSM-IV hierarchical
relationship between major depressive disorder and generalized anxiety disorder
and suggest that the exclusion criterion should be eliminated. Am J Psychiatry 2003 Mar;160(3):533-40
:
Pregabalin in generalized anxiety disorder: a placebo-controlled
trial.
Pande AC, Crockatt JG, Feltner DE, Janney CA, Smith WT, Weisler R,
Londborg PD, Bielski RJ, Zimbroff DL, Davidson JR, Liu-Dumaw M. OBJECTIVE: Current drug therapies for generalized anxiety disorder have
limitations. In a controlled trial, the novel agent pregabalin was studied for the
treatment of patients with generalized anxiety disorder. METHOD: In this
double-blind study, patients with DSM-IV generalized anxiety disorder were
randomly assigned to receive pregabalin (150 mg/day or 600 mg/day), lorazepam (6
mg/day), or placebo. A 1-week placebo lead-in was followed by 4 weeks of
treatment and then a 1-week dose taper. The primary efficacy measure was the
Hamilton Anxiety Rating Scale score at endpoint. RESULTS: A total of 276 patients
were randomly assigned to a treatment group and received at least one dose of their
assigned medication. Fewer patients given lorazepam (59%, N=40 of 68) completed
the trial than did those given placebo (73%, N=50 of 69), 600 mg/day of pregabalin
(71%, N=50 of 70), or 150 mg/day or pregabalin (90%, N=62 of 69). The mean
baseline-to-endpoint decreases in total Hamilton anxiety scale score in the patients
given 150 mg/day of pregabalin (-9.2), 600 mg/day of pregabalin (-10.3), and
lorazepam (-12.0) were significantly greater than the decrease in those given
placebo (-6.8). As early as the week 1 observation, pregabalin significantly reduced
the total Hamilton anxiety scale score compared with placebo. The most frequent
adverse events reported for pregabalin and lorazepam were somnolence and
dizziness. There were no serious adverse events reported by patients given
pregabalin, and no withdrawal syndrome was associated with pregabalin treatment.
CONCLUSIONS: These results indicate that pregabalin is an effective, rapidly
acting, and safe treatment for generalized anxiety disorder. In short-term
treatment, pregabalin does not appear to have the withdrawal symptoms associated
with the benzodiazepines. Am J Med Genet 2003 Feb 15;117B(1):1-6
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Association of a MAOA gene variant with generalized anxiety
disorder, but not with panic disorder or major depression.
Tadic A, Rujescu D, Szegedi A, Giegling I, Singer P, Moller HJ, Dahmen N.
Department of Psychiatry and Psychotherapy, University of Mainz, Mainz, Germany. This study was conducted to detect a possible association of a T941G single
nucleotide polymorphism (SNP) in the monoamine oxidase A (MAOA) gene with
generalized anxiety disorder (GAD), panic disorder (PD), or major depression (MD).
Fifty GAD patients (34 females and 16 males), 38 PD patients (21 females and 17
males), and 108 MD patients (80 females and 28 males) were included. The
comparison group consisted of 276 (132 females and 144 males) unrelated healthy
individuals. The 941T allele was over-represented in patients suffering from GAD
(chi(2) = 6.757; df = 1; P < 0.01, not corrected for multiple testing) when compared
to healthy volunteers. No association was observed in MD or PD. This is the first
study specifically analyzing the MAOA G941T polymorphism in GAD and thus needs
to be replicated in an independent sample. However, the results are in line with
previous data suggesting an association between the MAOA locus and regulation of
complex human behavior. Biol Psychiatry 2003 Feb 15;53(4):304-14
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Evidence for disturbed cortical signal processing and altered
serotonergic neurotransmission in generalized anxiety disorder.
Senkowski D, Linden M, Zubragel D, Bar T, Gallinat J.
Max-Planck-Institute of Cognitive Neuroscience, (DS), Leipzig, Germany Current pathophysiological concepts of generalized anxiety disorder (GAD) assume
a disturbed exteroceptive sensory system. Furthermore, central serotonergic
neurotransmission has been shown to play an important role in anxiety disorder.
Cortical signal processing as measured by auditory evoked potentials (AEPs) may
reflect the integrity of the exteroceptive sensory system. Because a special aspect
of AEP, the loudness dependence of the N1/P2-component (LD), has been related to
central serotonergic activity, the LD may be useful for investigating serotonergic
dysfunctions in GAD.The LD was recorded in 31 medication-free patients with GAD
without any psychiatric co-morbidity and in 31 matched control subjects. Dipole
source analysis was performed to separate the LD of regions including the primary
(LD-tangential dipole) and regions including the secondary auditory cortex
(LD-radial dipole).A shallower LD-tangential was observed in patients with GAD as
compared to healthy control subjects [F(1,60) = 6.727, p =.012; one-way analysis of
variance]. The LD-radial showed no differences between groups. Severity of the
anxiety symptoms was not related to the LDs.The results indicate an altered
exteroceptive sensory system in GAD occurring at the level of the primary but not
secondary auditory cortex. Because a shallow LD of the primary auditory cortex
was related to a high firing rate of neurons in the dorsal raphe nucleus, the results
may support evidence for an enhanced serotonergic activity in GAD. Actas Esp Psiquiatr 2002 Sep-Oct;30(5):287-91
:
[Paroxetine treatment for children and adolescents with anxiety
disorders]
[Article in Spanish]
Blasco-Fontecilla H, Madoz-Gurpide A, San Sebastian Cabases J, Calvo
Ablanedo R, Krauskopf Poblete V.
Unidad de Psiquiatria Infantil. Servicio de Psiquiatria. Hospital Ramon y Cajal.
Universidad de Alcala. Madrid. Spain. Background. Paroxetine has become an effectiveness treatment in anxiety
disorders in adults. Despite the fact that this is an especially prevalent
psychiatrist disorder in children and adolescents, there are very few studies in
this population. This study examines the effectiveness of paroxetine in children
and adolescents with anxiety disorders.Methodology. Fifteen children and
adolescents with ICD-criteria for anxiety disorder were selected. Anxiety
measurement was taken with STAI scale and was filled out before treatment and
6 months later (mean). We have used descriptive parameters and t Student test
for the analysis of dependent samples. Statistic work was done with SPSS
8.0.Results. On first testing, the mean score for State Factor was 41.8 (ds: 5.9)
and on second after treatment- it was 24.66 (ds: 9.8). Trait Factor was 43.53 (ds:
8.27) on first testing and 25 (ds: 8.91) on second. These differences in mean
scores for both State and Trait factors were significant (alpha=0.05, p=
0.000).Conclusions. Our results support the hypothesis of clinical improvement at
Anxiety Disorders in children and adolescent using Paroxetine. It seems logical to
continue the study increasing sample size and evaluation time. Int Clin Psychopharmacol 2002 May;17(3):103-7
:
Treatment of generalized anxiety disorder with citalopram.
Varia I, Rauscher F.
Department of Psychiatry and behavioural Sciences, Duke University Medical
Center, Durham, NC 27710, USA. varia001@mc.duke.edu Serotonin reuptake inhibitors (SSRI), such as venalafaxine and paroxetine, are
used in the treatment of generalized anxiety disorder (GAD). Patients with GAD
frequently have comorbid psychiatric disorders, such as depression. SSRIs are
effective in the treatment of a variety of anxiety disorders and depression.
Citalopram, a newer SSRI used in the treatment of depression, has not been
studied for GAD. This is the first report of the use of citalopram, the most
selective SSRI, for the treatment of GAD in a retrospective case observation
study. Thirteen patients diagnosed with GAD were treated with citalopram at an
academic outpatient clinic. The main outcome measures were the Hamilton Rating
Scale for Anxiety (HAM-A), Hamilton Depression Rating Scale (HAM-D) and
Clinical Global Impressions of Severity (CGI-S; at baseline) and Improvement
(CGI-I). The mean age of the patients was 38 years. The mean dose of citalopram
at endpoint was 33 mg/day (range 10-60 mg/day). After 12 weeks of treatment
with citalopram, all 13 patients experienced full or partial improvement in GAD and
depressive symptoms leading to meaningful improvement in social and occupational
functioning. Mean baseline HAM-A scores (mean+/-SEM) decreased from
22.2+/-1.3 to 6.2+/-0.9 after citalopram treatment. The mean CGI-I score was
1.8+/-0.2 with 11 of the 13 patients responding (CGI-I of 1 or 2). These data
suggest that citalopram may be an effective treatment for GAD. Several patients
who had failed previous treatment with other SSRIs responded to citalopram,
suggesting that a second SSRI, such as citalopram, may be beneficial in this
population. A larger placebo-controlled study of citalopram is warranted in GAD. CNS Drugs 2002;16(6):425-34
:
Spotlight on paroxetine in psychiatric disorders in adults.
Wagstaff AJ, Cheer SM, Matheson AJ, Ormrod D, Goa KL.
Adis International Limited, Auckland, New Zealand. demail@adis.co.nz Paroxetine is a selective serotonin reuptake inhibitor (SSRI), with
antidepressant and anxiolytic activity. In 6- to 24-week well designed trials,
oral paroxetine 10 to 50 mg/day was significantly more effective than placebo,
at least as effective as tricyclic antidepressants (TCAs) and as effective as
other SSRIs and other antidepressants in the treatment of major depressive
disorder. Relapse or recurrence over 1 year after the initial response was
significantly lower with paroxetine 10 to 50 mg/day than with placebo and
similar to that with imipramine 50 to 275 mg/day. The efficacy of paroxetine
10 to 40 mg/day was similar to that of TCAs and fluoxetine 20 to 60 mg/day in
6- to 12-week trials in patients aged > or = 60 years with major depression.
Paroxetine 10 to 40 mg/day improved depressive symptoms to an extent similar
to that of TCAs in patients with comorbid illness, and was more effective than
placebo in the treatment of dysthymia and minor depression. Paroxetine 20 to
60 mg/day was more effective than placebo after 8 to 12 weeks' treatment of
obsessive-compulsive disorder (OCD), panic disorder, social anxiety disorder
(social phobia), generalised anxiety disorder (GAD) and post-traumatic stress
disorder (PTSD). Improvement was maintained or relapse was prevented for 24
weeks to 1 year in patients with OCD, panic disorder, social anxiety disorder or
GAD. The efficacy of paroxetine was similar to that of other SSRIs in patients
with OCD and panic disorder and similar to that of imipramine but greater than
that of 2'chlordesmethyldiazepam in patients with GAD. Paroxetine is generally
well tolerated in adults, elderly individuals and patients with comorbid illness,
with a tolerability profile similar to that of other SSRIs. The most common
adverse events with paroxetine were nausea, sexual dysfunction, somnolence,
asthenia, headache, constipation, dizziness, sweating, tremor and decreased
appetite. In conclusion, paroxetine, in common with other SSRIs, is generally
better tolerated than TCAs and is a first-line treatment option for major
depressive disorder, dysthymia or minor depression. Like other SSRIs,
paroxetine is also an appropriate first-line therapy for OCD, panic disorder,
social anxiety disorder, GAD and PTSD. Notably, paroxetine is the only SSRI
currently approved for the treatment of social anxiety disorder and GAD,
which makes it the only drug of its class indicated for all five anxiety disorders
in addition to major depressive disorder. Thus, given the high degree of
psychiatric comorbidity of depression and anxiety, paroxetine is an important
first-line option for the treatment of major depressive disorder, OCD, panic
disorder, social anxiety disorder, GAD and PTSD. Drugs 2002;62(11):1635-48
:
Generalised anxiety disorder: treatment options.
Sramek JJ, Zarotsky V, Cutler NR.
Ingenix Pharmaceutical Services, Beverly Hills, California 90211, USA.
john.scramek@ingenix.com In recent years generalised anxiety disorder (GAD) has become a much better
defined disorder, with specific criteria distinguishing it from the other anxiety
disorders; however, it still lacks the same public and scientific interests as some
of the other anxiety disorders such as panic and social phobia. Nevertheless,
refinement in the treatment of GAD is becoming more evident through the
conduct of clinical trials. Up until the mid-1980's, treatment consisted primarily
of benzodiazepines. However, as a result of growing characterisation of their
abuse potential, other therapeutic options were explored. Benzodiazepines became
seen as an effective short-term therapy, and buspirone and some of the newer
antidepressants have become the treatment of choice for patients with GAD
requiring long-term treatment. Buspirone was the first available alternative to the
benzodiazepines in the US; however, the initial excitement over this agent was
somewhat dampened because of its mild efficacy combined with a slow onset of
action. The antidepressants were seen as beneficial for the treatment of GAD
because of the high comorbidity with depression, thus allowing a better outcome
for these patients. The antidepressants that offer both a good adverse effect
profile and efficacy are the selective serotonin reuptake inhibitors including
paroxetine, and the serotonin-norepinephrine reuptake inhibitors such as
venlafaxine. Clinicians should also consider the potential benefits of
psychotherapy as an adjunct to medication. There are a number of potentially new
pharmacotherapies being investigated, including newer serotonin 5-HT1A receptor
agonists, cholecystokinin receptor antagonists, neurokinin receptor antagonists,
gabapentin and its analogues, and gamma-aminobutyric acid (GABA)A receptor
modulators. However, these compounds are all in the early stages of investigation,
and there are no new therapies expected to be released in the near future.
Nonetheless, in the search for the ideal anxiolytic, a more positive outlook is
allowed by imminent future research for new treatment options in patients with
GAD. J Clin Psychiatry 2002;63 Suppl 8:17-23
:
Treatment of generalized anxiety disorder.
Gorman JM.
Department of Psychiatry, Columbia University, New York, NY 10032, USA.
jmg9@columbia.edu Generalized anxiety disorder (GAD) is characterized by chronic worry that may
persist for many years. It is a debilitating disorder, and effective long-term
treatment is required. Psychotherapy, particularly relaxation, cognitive therapy,
and cognitive-behavioral therapy, has shown long-term benefit in GAD and may be
a useful approach alone and as an adjunct to pharmacotherapeutic options.
Available medications for GAD include benzodiazepine anxiolytics, buspirone, and
antidepressants. Although benzodiazepines are effective as short-term
anxiolytics, their use is compromised by a poor adverse event profile and, like
buspirone, they lack the antidepressant efficacy important for addressing the
comorbid depression experienced by many patients with GAD. Antidepressants,
including paroxetine and the serotonin-norepinephrine reuptake inhibitor
venlafaxine, are effective anxiolytics and resolve symptoms of depression in
patients with GAD. The benefit of venlafaxine is sustained long term, enabling
increased numbers of patients to attain remission from symptoms and experience
restoration of normal functioning. Although further clinical studies are required
to establish the use of psychosocial therapy in the treatment of GAD. preliminary
results are encouraging. At present, the use of psychosocial therapy and
second-generation antidepressants, such as some selective serotonin reuptake
inhibitors and venlafaxine, offer the best approach to attaining long-term benefit
for patients with GAD. J Clin Psychiatry 2002;63 Suppl 8:35-42
:
Generalized anxiety disorder in primary care: emerging issues in
management and treatment.
Culpepper L.
Boston University, Mass. 02118, USA. larry.culpepper@bmc.org Generalized anxiety disorder (GAD) is highly prevalent in primary care patients
and is a source of major morbidity. The low rate of recognition and diagnosis of
GAD is often the result of insufficient knowledge on the part of primary care
physicians, time pressures, and competing demands during patients' visits. Patient
attribution of symptoms and the stigma related to mental illness also contribute to
underrecognition. Other contributing factors include the natural history of GAD,
the bimodal age of presentation, a chronic but waxing and waning course, frequent
comorbidity with other anxiety and depressive disorders, and the controversy
regarding the best diagnostic criteria. However, proper diagnosis is critical to
appropriate management. Primary care management of GAD and associated
comorbidities includes education about the nature of GAD as a medical disorder
that is amenable to treatment and counseling about treatment alternatives and
coping strategies. Most patients with GAD suffer from insomnia, and treating
insomnia can be of great benefit to them. While cognitive-behavioral therapy and
relaxation therapy are effective in treating GAD, most patients in primary care
settings are likely to require pharmacologic treatment. Although commonly used,
benzodiazepines and their short-term benefits are overshadowed by their
decreased long-term effectiveness, their minimal treatment of psychic symptoms,
and their degradation of patient performance. The selective serotonin reuptake
inhibitor (SSRI) paroxetine is indicated for the short-term treatment of GAD,
although adequate data supporting the use of most SSRIs for GAD are not yet
available. The serotonin-norepinephrine reuptake inhibitor venlafaxine provides a
treatment option resulting in both short- and long-term improvement of symptoms,
attaining not only a response but also remission from GAD and prevention of
relapse. Prescrire Int 2001 Oct;10(55):131-4
:
Venlafaxine and generalised anxiety disorder: new preparation.
Minimise recourse to drugs.
(1) Generalised anxiety disorder is defined as excessive anxiety for at least 6
months. (2) Management is based primarily on psychological measures, with the aim
of limiting recourse to drugs. The reference drugs are benzodiazepines. The
treatment period should be as short as possible, to avoid adverse effects such as
sedation and dependence. (3) Venlafaxine is a non tricyclic, non MAOI
antidepressant. A sustained-release formulation has just been granted marketing
authorisation in France for generalised anxiety disorder. (4) The clinical
assessment file on venlafaxine in this indication includes results from two 8-week
trials and a placebo-controlled trial with 6 months follow-up. The trials showed a
significant improvement with venlafaxine on standard anxiety scales, but the
clinical impact (at best moderate) has been poorly assessed. We found no
comparison between venlafaxine and benzodiazepines. (5) In one trial venlafaxine
was no more effective than buspirone. (6) The most frequent adverse effects of
venlafaxine are gastrointestinal disorders, insomnia and dizziness. Venlafaxine
carries a risk of drug interactions and withdrawal symptoms. (7) In practice,
venlafaxine provides nothing new in the treatment of generalised anxiety disorder.
The reference drug treatment remains a benzodiazepine. J Clin Psychiatry 2001 May;62(5):350-7
:
Erratum in:
J Clin Psychiatry 2001 Aug;62(8):658
Paroxetine in the treatment of generalized anxiety disorder:
results of a placebo-controlled, flexible-dosage trial.
Pollack MH, Zaninelli R, Goddard A, McCafferty JP, Bellew KM, Burnham
DB, Iyengar MK.
Department of Psychiatry, Massachusetts General Hospital, Harvard Medical
School, Boston 02114, USA. MPOLLACK@partners.org CONCLUSION: Paroxetine in doses of 20 to 50
mg once daily is effective in the treatment of patients with GAD. Improvement of
core symptoms of GAD occurs early and is associated with significant reduction in
disability after only 8 weeks of treatment. Am J Manag Care 2001 Sep;7(11 Suppl):S367-76
:
Recent perspectives on the diagnosis and treatment of
generalized anxiety disorder.
Ninan PT. Anxiety disorders are common mental disorders, encompassing a group of
conditions that share extreme or pathological anxiety as the primary disturbance
in mood or emotional tone. Anxiety disorders include generalized anxiety disorder
(GAD), panic disorder, agoraphobia, specific phobias, social anxiety disorder,
obsessive-compulsive disorder, and posttraumatic stress disorder. Individual
anxiety disorders have considerable symptomatic overlap in their expression. The
life-time prevalence of all anxiety disorders in the general population is about
25%. There is familial aggregation of anxiety and mood disorders such as major
depression. Genetic factors and life experiences both contribute to the likelihood
of developing anxiety disorders. GAD is characterized by excessive anxiety and
uncontrollable worry, is present for longer than 6 months, and tends to occur
comorbidly with other conditions, including other anxiety disorders and major
depression as well as general medical conditions. GAD, given its chronic nature, is
associated with significant impairment. GAD is responsive to pharmacological
treatments, such as anxiolytics and antidepressants, as well as psychotherapies
such as cognitive therapy. Med Clin North Am 2001 May;85(3):691-710
:
Generalized anxiety disorder. An important clinical concern.
Hidalgo RB, Davidson JR.
Department of Psychiatry and Behavioral Sciences, Duke University, Durham,
North Carolina, USA. GAD is common, often follows a chronic course, and usually is associated with
extensive psychiatric and medical comorbidity. This disorder often presents in a
primary care setting, commonly with somatic symptoms; it is important for primary
care physicians to be aware of its existence, forms of presentation, and different
treatments. GAD appears to be twice as common in women than men. There is some
evidence that the neurobiologic basis of GAD may involve abnormalities in
neurochemical, neuroendocrine, neurophysiologic, and neuroanatomic factors.
Research on psychosocial treatment of GAD has favored the combination of
cognitive therapy and relaxation techniques or anxiety management training. It
also appears that relapse rates after termination of cognitive-behavioral therapy
are low. Taking into consideration that GAD generally is chronic and associated
frequently with depressive symptoms, the ideal pharmacotherapy may be a drug
that can treat these comorbid disorders adequately. New antidepressants,
especially those with action in the serotonin system and possibly noradrenergic,
may be the appropriate option: They not only treat anxiety, but also treat or
prevent the development of comorbid depression; they should be effective ideally
during prolonged periods without risks related to addiction or withdrawal, such as
may happen with benzodiazepines and some antidepressants. The role of newly
emerging drugs, such as some anticonvulsants, in GAD needs to be defined more
clearly. More research is warranted to address issues such as (1) whether
pharmacotherapy is as effective, less effective, or more effective than
cognitive-behavioral therapy; (2) whether antidepressants improve the rate of
wellness or remission; and (3) whether prolonged antidepressant therapy for GAD
protects against later emergent depression. J Clin Psychopharmacol 2001 Feb;21(1):59-65
:
Opipramol for the treatment of generalized anxiety disorder: a
placebo-controlled trial including an alprazolam-treated group.
Moller HJ, Volz HP, Reimann IW, Stoll KD.
Psychiatrische Klinik der Ludwig-Maximilians-Universitat, Munich, Germany. Opipramol, a drug widely prescribed in Germany, is a tricyclic compound with no
reuptake-inhibiting properties. However, it has pronounced D2-, 5-HT2-, and
H1-blocking potential and high affinity to sigma receptors (sigma-1 and sigma-2).
In early controlled trials, anxiolytic effects were revealed. However, those
studies were performed before the concept of generalized anxiety disorder
(GAD) was established. Because of the interesting receptor-binding profile and
promising results of the early clinical trials, the authors performed a
state-of-the-art placebo-controlled trial using alprazolam as an active control.
Three hundred seven outpatients with GAD were included. After a 7-day
single-blind placebo washout, patients were randomly assigned to receive either
opipramol (final dose, 200 mg/day), alprazolam (2 mg/day), or placebo and were
treated for 28 days. The efficacy of both active compounds was higher than the
effects with placebo treatment. There were statistically significant differences
(p < 0.05, according to the analysis of covariance) in the main outcome criterion
(baseline-adjusted final means of an intent-to-treat analysis of the total scores
on the Hamilton Rating Scale for Anxiety) and in secondary efficacy parameters,
with global improvement of 47% for placebo and significantly more for opipramol
(63%) and alprazolam (64%). Regarding safety and tolerability, no substantial
differences in the number of adverse events observed between treatment groups
were obvious. Sedation seemed more pronounced with alprazolam treatment than
with opipramol or placebo. In this trial, it was demonstrated for the first time
that opipramol, a strong but nonselective sigma site ligand, possesses anxiolytic
efficacy superior to placebo in the treatment of GAD.Clin Cornerstone 2001;3(3):37-46
:
Generalized anxiety disorder.
Gorman JM.
Department of Psychiatry, College of Physicians and Surgeons of Columbia
University, New York, New York, USA. The diagnosis of generalized anxiety disorder (GAD) was first introduced in 1980
with the publication of the Diagnostic and Statistical Manual of Mental Disorders,
Third Edition (DSM-III) of the American Psychiatric Association. Prior to this,
the diagnosis of "anxiety neurosis" was given to patients with symptoms similar to
those now incorporated within the GAD category. Originally, GAD was created as
a residual category within the anxiety disorders as a rubric for patients with
serious anxiety problems but without panic attacks. Panic disorder therefore
received far more research attention, and GAD was seen as a diagnosis of
exclusion once panic disorder had been ruled out. It is now clear, however, that
GAD is a serious psychiatric disorder that is more common than panic disorder and
frequently encountered in primary care practice. Indeed, the primary care
physician is more likely to see patients with pure GAD than is the psychiatrist.
While the treatment of GAD is relatively straightforward, the diagnosis can be
difficult. Hence, careful attention to several key symptomatic presentations is
important.J Clin Psychiatry 2000 Feb;61(2):91-4
R:
Comment in:
J Clin Psychiatry. 2001 Aug;62(8):657-8.
Prior benzodiazepine use and buspirone response in the
treatment of generalized anxiety disorder.
DeMartinis N, Rynn M, Rickels K, Mandos L.
Department of Psychiatry, University of Pennsylvania, Philadelphia 19104-2649,
USA. BACKGROUND: An earlier preliminary report suggested that prior treatment with
benzodiazepines might predict a reduced response to buspirone in patients
diagnosed with generalized anxiety disorder (GAD). To confirm or refute this
hypothesis, the present data analysis was conducted. METHOD: One large data
set (N = 735) of GAD patients (DSM-III) treated with buspirone, a
benzodiazepine, and a placebo was analyzed by dividing all patients into 3 prior
benzodiazepine (BZ) treatment groups: no prior BZ treatment, recent (< 1 month)
BZ treatment, and remote (> or = 1 month) BZ treatment. Using an intent-to-treat
last-observation-carried-forward (LOCF) data set, acute 4-week treatment
response was assessed in terms of clinical improvement, attrition, and adverse
events as a function of these 3 prior benzodiazepine treatment groups. RESULTS:
Patient attrition was significantly higher (p < .05) in the recent BZ treatment
group than in the remote and no prior BZ treatment groups with lack of efficacy
given as the primary reason by patients receiving buspirone but not
benzodiazepine or placebo. In the buspirone group, adverse events occurred more
frequently in the recent BZ treatment group than in the remote BZ treatment and
no prior BZ treatment groups. Finally, clinical improvement with buspirone was
similar to benzodiazepine improvement in the no prior BZ treatment and remote BZ
treatment groups, but less than benzodiazepine improvement in the recent BZ
treatment group, leading to the smallest buspirone/placebo differences in
improvement in the recent BZ treatment group. CONCLUSION: These data
suggest that the initiation of buspirone therapy in GAD patients who have only
recently terminated benzodiazepine treatment should be undertaken cautiously
and combined with appropriate patient education.Depress Anxiety 2000;12 Suppl 1:81-4
:
Efficacy, safety, and tolerability of venlafaxine XR in
generalized anxiety disorder.
Kelsey JE.
Department of Psychiatry and Behavioral Sciences, Emory University School of
Medicine, Atlanta, Georgia 30329, USA. jkels01@emory.eduGeneralized anxiety disorder (GAD) is a common and chronic disorder with a low
rate of spontaneous remission. A complication in treatment selection is the high
rates of co-morbid major depressive disorder in this population. A number of
treatments exist to treat GAD. The most recent medication to gain an indication
for GAD is venlafaxine XR, a serotonin/norepinephrine reuptake inhibitor that is
also approved for the treatment of major depressive disorder. More than 2,000
patients with GAD have been studied in outpatient trials of venlafaxine XR with
demonstrated efficacy, tolerability and safety of this compound. This article
reviews these studies, both short term and longer (6 month) continuation trials.
The response to venlafaxine XR in this population, combined with good tolerability,
makes this agent an appropriate first-line medication for GAD. In general,
treatment with antidepressants, though associated with a longer onset of action
than benzodiazepines, does not produce physiological dependency, and is useful in
a patient population with a high prevalence of mood disorders.Effexor (Venlafaxine)-
75 mg-
100-
$136.25
Effexor (Venlafaxine) -
37.5 mg-
100-
$73.13
Effexor XR (Venlafaxine XR) -
150 mg-
100-
$153.57
Effexor XR (Venlafaxine XR) -
75 mg-
100-
$136.25
Effexor XR (Venlafaxine XR)-
37.5 mg-
100-
$73.13 Paxil (Paroxetine)-
30 mg-
90-
$145.64
Paxil (Paroxetine)-
20 mg-
100-
$147.84
Paxil (Paroxetine) -
10 mg-
90-
$142.88 Buspirone (Buspar)-
10 mg-
100-
$92.44
Buspirone (Generic) -
10 mg-
100-
$61.24
