Paroxetine: an update of its use in psychiatric disorders in adults

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.     

Spotlight on paroxetine in psychiatric disorders in adults

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.     

Escitalopram: a review of its use in the management of anxiety disorders

Escitalopram (Cipralex, Lexapro, Seroplex, Sipralexa), the therapeutically active S-enantiomer of racemic citalopram (RS-citalopram), is a potent and highly selective serotonin reuptake inhibitor. It is effective and generally well tolerated in the treatment of moderate to severe generalised anxiety disorder (GAD) or social anxiety disorder (SAD), panic disorder (with or without agoraphobia) as well as obsessive-compulsive disorder (OCD). Moreover, escitalopram is at least as effective as paroxetine for the treatment of GAD, SAD or OCD and appears to achieve a more rapid response than racemic citalopram in the management of panic disorder. Generally, it has a more favourable tolerability profile than paroxetine in terms of fewer discontinuation symptoms. In addition, a favourable pharmacokinetic profile permits once-daily administration of the drug. Additional comparative studies are required to definitively position escitalopram with respect to other SSRIs and venlafaxine. Nevertheless, available clinical data indicate that escitalopram is an effective first-line treatment option for the management of GAD, SAD, panic disorder and OCD.     

A double blind comparison of venlafaxine and paroxetine in obsessive-compulsive disorder

SUMMARY: While the usefulness of clomipramine and selective serotonin reuptake inhibitors (SSRIs) in obsessive-compulsive disorder (OCD) has been established, the efficacy of serotonin-norepinephrine reuptake inhibitors remains to be determined. This report describes the first randomized double-blind comparison study of an SNRI in patients with obsessive-compulsive disorder. The current study compares the efficacy and tolerability of venlafaxine with paroxetine. One hundred and fifty patients with primary OCD according to DSM-IV criteria were randomly assigned in a 12-week double-blind trial to receive dosages titrated upward to 300 mg/d of venlafaxine (n = 75) or 60 mg/d of paroxetine (n = 75). Primary efficacy was assessed by the change from baseline on the Yale-Brown obsessive-compulsive scale (Y-BOCS). Other assessments throughout the trial included the Hamilton depression rating scale, and the Hamilton anxiety rating scale. An intent-to-treat, last-observation-carried-forward analysis demonstrated a mean decrease on the Y-BOCS of 7.2 +/- 7.5 in the venlafaxine group and of 7.8 +/- 5.4 in the paroxetine group. In both treatment groups, a responder rate (decrease > 35% on the Y-BOCS) of approximately 40% was found. There were no significant differences between venlafaxine and paroxetine with regard to response or responder rates. The incidence of adverse events for venlafaxine and paroxetine was comparable. The most common side effects for venlafaxine were somnolence, insomnia, a dry mouth, and sweating; and for paroxetine somnolence, sweating, nausea, and headache. These results show that venlafaxine was equally effective to paroxetine in treating patients with OCD. Venlafaxine may be a useful therapy for obsessive-compulsive patients, but is not superior to SSRIs.     

Fluvoxamine. An updated review of its use in the management of adults with anxiety disorders

Fluvoxamine is a potent and selective serotonin reuptake inhibitor (SSRI) that has little or no effect on other monoamine reuptake mechanisms. Relative to other SSRIs, fluvoxamine is a weak inhibitor of cytochrome P450 (CYP) 2D6, a moderate inhibitor of CYP2C19 and CYP3A4 and a potent inhibitor of CYP1A2. In randomised, double-blind trials. fluvoxamine 100 to 300 mg/day for 6 to 10 weeks significantly reduced symptoms of obsessive-compulsive disorder (OCD) compared with placebo. Response rates of 38 to 52% have been reported with fluvoxamine, compared with response rates of 0 to 18% with placebo. In patients with OCD, fluvoxamine had similar efficacy to that of clomipramine and, in smaller trials, the SSRIs paroxetine and citalopram and was significantly more effective than desipramine. Maintenance therapy with fluvoxamine may reduce the likelihood of relapses in up to 67% of patients with OCD. Fluvoxamine < or = 300 mg/day for 6 to 8 weeks was as effective as imipramine in patients with panic disorder, and significantly more effective than placebo. In addition, treatment with fluvoxamine < or = 300 mg/day for > or = 8 weeks improved symptoms of social phobia (social anxiety disorder), post-traumatic stress disorder (PTSD), pathological gambling, compulsive buying, trichotillomania, kleptomania, body dysmorphic disorder, eating disorders and autistic disorder. Large trials comparing the efficacy of fluvoxamine and other SSRIs in patients with anxiety disorders are warranted. Fluvoxamine is generally well tolerated; in postmarketing studies, nausea was the only adverse event occurring in >10% of patients with less commonly reported events including somnolence, asthenia, headache, dry mouth and insomnia. Fluvoxamine is associated with a low risk of suicidal behaviour, sexual dysfunction and withdrawal syndrome. Fewer anticholinergic or cardiovascular events are associated with fluvoxamine than tricyclic antidepressants. Although comparative data are lacking, the tolerability profile of fluvoxamine appears to be broadly similar to those of other SSRIs. CONCLUSION: Fluvoxamine has demonstrated short term efficacy in the treatment of OCD, panic disorder, social phobia, PTSD and in a range of obsessive-compulsive spectrum disorders. The drug is as effective as clomipramine in patients with OCD but appears to have a better tolerability profile. On the basis of current treatment guidelines, fluvoxamine, like other SSRIs, is recommended as first-line treatment for a number of anxiety disorders. It appears to offer some pharmacokinetic advantages and a different drug interaction profile to the other SSRIs with a broadly similar spectrum of adverse events. However, direct comparisons are required to assess the relative efficacy and tolerability of the different agents of this drug class.     

Paroxetine: safety and tolerability issues

Paroxetine is a selective serotonin re-uptake inhibitor (SSRI) available in immediate release and controlled release (CR) formulations. Paroxetine is the most potent inhibitor of serotonin re-uptake among the now available SSRIs. Paroxetine has been approved for the treatment of major depressive disorder (MDD), obsessive–compulsive disorder, panic disorder (PD), generalised anxiety disorder, post traumatic stress disorder (PTSD), and social anxiety disorder (SAD) in adults, whereas paroxetine CR is approved for the treatment of MDD, SAD, PD and premenstrual dysphoric disorder in adults. The overall efficacy of paroxetine seems to be comparable to other SSRIs in the treatment of approved indications, although paroxetine treatment induces more sedation, constipation, sexual dysfunction, discontinuation syndrome and weight gain than other SSRIs. Recent data suggest that paroxetine treatment leads to increased rates of congenital malformations, although this evidence is not conclusive. Paroxetine and paroxetine CR are not indicated for use in the paediatric population and are categorised as Pregnancy Class D. In conclusion, whether the tolerability profile of paroxetine differs substantially from other new antidepressants (including other SSRIs) needs to be determined in adequately powered well-designed randomised controlled comparative clinical trials.     

Paroxetine: safety and tolerability issues

Paroxetine is a selective serotonin re-uptake inhibitor (SSRI) available in immediate release and controlled release (CR) formulations. Paroxetine is the most potent inhibitor of serotonin re-uptake among the now available SSRIs. Paroxetine has been approved for the treatment of major depressive disorder (MDD), obsessive-compulsive disorder, panic disorder (PD), generalised anxiety disorder, post traumatic stress disorder (PTSD), and social anxiety disorder (SAD) in adults, whereas paroxetine CR is approved for the treatment of MDD, SAD, PD and premenstrual dysphoric disorder in adults. The overall efficacy of paroxetine seems to be comparable to other SSRIs in the treatment of approved indications, although paroxetine treatment induces more sedation, constipation, sexual dysfunction, discontinuation syndrome and weight gain than other SSRIs. Recent data suggest that paroxetine treatment leads to increased rates of congenital malformations, although this evidence is not conclusive. Paroxetine and paroxetine CR are not indicated for use in the paediatric population and are categorised as Pregnancy Class D. In conclusion, whether the tolerability profile of paroxetine differs substantially from other new antidepressants (including other SSRIs) needs to be determined in adequately powered well-designed randomised controlled comparative clinical trials.     

Serotonergic drugs in the treatment of depressive and anxiety disorders

Serotonergic dysfunction has been implicated in the aetiology of several psychiatric conditions, including depressive and anxiety disorders. Much of the evidence for the role of serotonin (5-HT) in these disorders comes from treatment studies with serotonergic drugs, including selective serotonin reuptake inhibitors (SSRIs), 5-HT(1A) agonists and 5-HT antagonists. This review considers the place of these drugs in the treatment of panic disorder, obsessive-compulsive disorder (OCD), social phobia, and generalized anxiety disorder (GAD). Among these agents, the SSRIs stand out with proven efficacy in the treatment of a spectrum of disorders, such as depression, panic disorder, OCD and social phobia. They may also be a suitable treatment for GAD. 5-HT(1A) agonists have been used extensively for the treatment of depression and GAD but evidence of their efficacy in other anxiety disorders is equivocal. 5-HT antagonists are the least well studied of these agents: while they may have activity in depression, their efficacy has not been fully investigated in anxiety disorders. However, preliminary reports suggest that they may be useful as adjuvants to SSRIs in treatment-refractory OCD. The high incidence of comorbidity amongst psychiatric disorders means that pharmacotherapy that is effective against a range of disorders, such as the SSRIs, is of considerable use to clinicians. Future research into the biological mechanisms underlying such disorders is likely to further enhance pharmacotherapy. Copyright 2000 John Wiley & Sons, Ltd.     

Localized orbitofrontal and subcortical metabolic changes and predictors of response to paroxetine treatment in obsessive-compulsive disorder.

Previous positron emission tomography (PET) studies of patients with obsessive-compulsive disorder (OCD) have found elevated glucose metabolic rates in the orbitofrontal cortex (OFC) and caudate nuclei that normalize with response to treatment. Furthermore, OCD symptom provocation differentially activates specific subregions of the OFC, which have distinct patterns of connectivity and serve different functions. Therefore, we sought to determine the role of specific subregions of the OFC and associated subcortical structures in mediating OCD symptoms, by determining how glucose metabolism in these structures changed with paroxetine treatment of OCD patients. We also sought to determine whether pretreatment OFC metabolism would predict response to paroxetine, as it has for other OCD treatments. Twenty subjects with OCD received [18F]-fluorodeoxyglucose (FDG)-PET scans before and after 8 to 12 weeks of treatment with paroxetine, 40 mg/day. In patients who responded to paroxetine, glucose metabolism decreased significantly in right anterolateral OFC and right caudate nucleus. Lower pretreatment metabolism in both left and right OFC predicted greater improvement in OCD severity with treatment. These results add to evidence indicating that orbitofrontal-subcortical circuit function mediates the symptomatic expression of OCD. Specific subregions of the OFC may be differentially involved in the pathophysiology of OCD and/or its response to pharmacotherapy.     

氟伏沙明与帕罗西汀治疗强迫症的对照研究

目的比较氟伏沙明与帕罗西汀治疗强迫症的疗效及安全性。方法分别用氟伏沙明和帕罗西汀治疗强迫症患者各36例，采用Yale—Brown强迫量表、汉密尔顿抑郁量表（HAMD）及不良反应量表（TESS）评定疗效和不良反应。结果氟伏沙明和帕罗西汀疗效相似，差异无统计学意义，氟伏沙明起效慢于帕罗西汀，其不良反应也少于帕罗西汀。结论氟伏沙明治疗强迫症安全有效，值得推广。     

The effects of tianeptine or paroxetine on 35% CO2 provoked panic in panic disorder

Antidepressants that inhibit the reuptake of serotonin (5-HT) are particularly effective in the treatment of panic disorder. Evidence suggests that increased 5-HT availability is important for the anti-panic effect of serotonergic drugs and in maintaining the response to selective serotonin reuptake inhibitors (SSRIs). Tianeptine is an antidepressant with 5-HT reuptake enhancing properties (i.e. the opposite pharmacological profile to that of SSRIs). Therefore, no effect would be expected in panic disorder. The aim of the present study was to compare the effect of tianeptine with that of paroxetine, a selective 5-HT reuptake inhibitor with demonstrated efficacy in panic disorder, on the vulnerability to a laboratory panic challenge in panic disorder patients. Twenty panic disorder patients were treated with either tianeptine or paroxetine for a period of 6 weeks, in a randomized, double-blind, separate group design. The reaction to a 35% CO(2) panic challenge was assessed at baseline and after treatment. Improvement on several clinical scales was also monitored. Tianeptine, as well as paroxetine, showed a significant reduction in vulnerability to the 35% CO(2) panic challenge. In spite of their opposite influence on 5-HT uptake, both tianeptine and paroxetine appeared to reduce the reaction to the panic challenge. These results raise questions about the necessity of 5-HT uptake for the therapeutic efficacy of anti-panic drugs.     

Treatment of panic disorder: focus on paroxetine

Panic disorder is a chronic and disabling condition associated with significant morbidity. Treatment of panic disorder has evolved significantly in the past 20 years with the availability of serotonergic antidepressants, including the selective serotonin reuptake inhibitors (SSRIs). Of these, paroxetine was the first to receive an indication for treatment of panic disorder and has been extensively studied in this area. A series of randomized, double-blind, placebo-controlled studies have demonstrated the efficacy and safety of paroxetine treatment of panic disorder, with a majority of patients achieving panic-free status during 12-week studies. Continued treatment with paroxetine results in sustained rates of remission compared with placebo. The combination of paroxetine and cognitive behavioral therapy appears to offer benefits of efficacy and sustained therapeutic response.     

11-year-old boy with panic disorder responding to paroxetine

We experienced an 11-year-old boy with panic disorder responding remarkably to paroxetine. Only a few studies have reported the clinical application of selective serotonin reuptake inhibitors (SSRIs) on children with panic disorder. In Japan, there are reports of child depression, autism, and school phobia; no study has focused on paroxetine treatment for children with panic disorder. Therefore, the case is discussed in this study.     

Selective serotonin reuptake inhibitors in the treatment of paediatric anxiety disorders: a review

Anxiety disorders (obsessive-compulsive disorder, social phobia/selective mutism, panic disorder, separation anxiety, generalized anxiety disorder, simple phobia and post-traumatic stress disorder) are the most prevalent psychiatric disorders in children and adolescents. The selective serotonin reuptake inhibitors (SSRIs)--citalopram, fluoxetine, fluvoxamine, paroxetine and sertraline--have demonstrated efficacy in treating anxiety disorders in adults. Although less information is available on the use of these agents in the paediatric population, research into the SSRIs for childhood anxiety disorders is increasing. This article reviews current literature, including case reports as well as open and controlled trials, on the effectiveness and tolerability of the SSRIs in the paediatric population. It also discusses developmental differences in children that should be considered in the utilisation of the SSRIs in paediatric patients.     

Paroxetine treatment of generalized anxiety disorder

Generalized anxiety disorder (GAD) is a prevalent and disabling anxiety disorder, conservatively believed to affect at least 5% of the general population. Cardinal symptoms of GAD include chronic and uncontrollable worry, anxiety, and tension, which result in difficulty fulfilling social, professional, and family roles. Treatment options include benzodiazepines, tricyclic antidepressants (TCAs), selective serotonin reuptake inhibitors (SSRIs), and the serotonin-norepinephrine reuptake inhibitor (SNRI) venlafaxine XR. Because of the high comorbidity of GAD with other psychiatric disorders, pharmacologic therapy should possess both anxiolytic and antidepressive properties for best outcomes. The SSRIs are a good treatment option, and paroxetine is the best studied SSRI for GAD and the only SSRI to date approved by the US Food and Drug Administration for this indication. Results of randomized, controlled studies of paroxetine have demonstrated its efficacy in the short-term treatment of GAD, in achieving and sustaining full remission, and in preventing relapse. This article provides an overview of GAD and a discussion of studies of paroxetine treatment in this anxiety disorder.     

Association study of the serotonin transporter gene polymorphism in obsessive-compulsive disorder

The hypothesis implicating the serotonergic system in the pathophysiology of obsessive-compulsive disorder (OCD) is supported by the therapeutic efficacy of selective serotonin reuptake inhibitors (SSRIs). Since SSRIs act on the serotonin transporter (5-HTT), it has been suggested that the 5-HTT gene (SCL6A4) could be a good candidate for OCD. The SCL6A4 gene has a 44-bp insertion/deletion polymorphism in its promoter region (5-HTTLPR). Previous studies have revealed an association between OCD and the l allele. We analysed the 5-HTTLPR polymorphic system in 115 Mexican OCD patients and 136 controls. No significant association was found between l allele and OCD (chi2 = 1.54, d.f. = 1, p = 0.21). Furthermore, we assessed alternative methods that employ family-based designs in a sample of 43 trios. Haplotype-based haplotype relative risk and transmission disequilibrium analysis did not show a preferential transmission of l allele to OCD probands. Our results indicate the need to analyse larger samples using family-based methods.     

喹硫平早期辅助治疗对首诊强迫症患者脱落率的影响

目的:研究早期联合喹硫平( quetiapine,QUE)治疗对首诊强迫症(obsessive-compulsive disorder,OCD)药物治疗脱落率的影响.方法:对146例门诊首诊并且接受5-羟色胺再摄取抑制剂 (selective serotonin reuptake inhibitors ,SSRIs)治疗的OCD患者进行回顾性研究,调查一般资料、治疗前症状自评量表(SCL-90)评分、首诊药物方案、脱落情况,按照首诊药物方案分为SSRIs组(108例)和SSRIs+QUE组(38例).脱落定义为在12周之前终止治疗.通过二元Logistic回归分析了解脱落的影响因素.结果:首诊SSRIs+QUE组的脱落率为34.2％(13/38),SSRIs组脱落率为70.4％(76/108),差异具有统计学意义(x2=15.44,P＜0.01).回归分析结果显示,脱落的发生和首诊药物方案、治疗前强迫症状严重程度相关,首诊联合喹硫平治疗可降低脱落率(Wals=10.041,P＜0.01),治疗前强迫症状轻的患者更容易发生脱落(Wals=8.196,P＜0.01).结论:首诊联合喹硫平可降低OCD患者的脱落率,使得更多的患者从随后的治疗中获益.     

Selective serotonin reuptake inhibitors in the treatment of panic disorder and agoraphobia

This review article summarizes comparator-controlled, short-term studies with currently available selective serotonin reuptake inhibitors (SSRIs) in the treatment of panic disorder and agoraphobia. Fluvoxamine, fluoxetine, paroxetine, sertraline and citalopram have all been proven to be superior to pill-placebo in the treatment of panic disorder, agoraphobia and associated symptoms such as depression. Direct comparisons with other antidepressants, benzodiazepines, cognitive-behavioural therapies or combinations of SSRIs with psychotherapeutic interventions are scarce. The majority of studies have reported on fluvoxamine whereas, to date, sertraline and citalopram have been compared only with placebo. Meta-analyses have suggested that combining an antidepressant with exposure in vivo produces the greatest treatment gains. Since this procedure is already commonly used in everyday clinical practice, it is recommended that future research in the treatment of panic disorder be directed towards the investigation of a combination of SSRIs with exposure therapy.     

Amygdala volume reductions in pediatric patients with obsessive-compulsive disorder treated with paroxetine: preliminary findings.

The amygdala is believed to be highly relevant to the pathophysiology of obsessive-compulsive disorder (OCD) given its prominent role in fear conditioning and because it is an important target of the serotonin reuptake inhibitors (SRIs), the pharmacotherapy of choice for OCD. In the present study, we measured in vivo volumetric changes in the amygdala in pediatric patients with OCD following 16 weeks of monotherapy with the selective SRI, paroxetine hydrochloride. Amygdala volumes were computed from contiguous 1.5 mm magnetic resonance (MR) images in 11 psychotropic drug-naive patients with OCD prior to and then following treatment. Eleven healthy pediatric comparison subjects also had baseline and follow-up scans, but none of these subjects received medication. Patients demonstrated significant asymmetry of the amygdala (L>R) prior to pharmacologic intervention in contrast to healthy comparison subjects who showed no asymmetry at the time of their baseline scan. Mixed model analyses using age and total brain volume as time varying covariates indicated that left amygdala volume decreased significantly in patients following treatment. The reduction in left amygdala volume in patients correlated significantly with higher paroxetine dosage at the time of the follow-up scan and total cumulative paroxetine exposure between the scans. No significant changes in either right or left amygdala volume were evident among healthy comparison subjects from the baseline to the follow-up scan. These preliminary findings suggest that abnormal asymmetry of the amygdala may play a role in the pathogenesis of OCD and that paroxetine treatment may be associated with a reduction in amygdala volume.