An open trial of fluoxetine in the treatment of panic attacks

Fluoxetine is a new antidepressant with pharmacologic effects apparently limited to blockade of neuronal serotonin reuptake. We entered 20 patients who met DSM-III criteria for either panic disorder or agoraphobia with panic attacks into an open, uncontrolled pilot study of fluoxetine. Four responded to placebo in the week before fluoxetine administration and were dropped from the study. Of the remaining 16 patients, nine were nonresponders and seven were responders, with complete cessation of their panic attacks. Eight of the nine nonresponders were unable to tolerate the side effects of fluoxetine. In contrast, all of the responders (and one nonresponder) experienced minimal side effects. Fluoxetine may be effective in the treatment of panic attacks, perhaps implicating the serotonergic system in the pathophysiology of panic disorder. Future studies should use very low doses of fluoxetine to initiate treatment.     

Do antidepressants selectively suppress spontaneous (unexpected) panic attacks? A replication

The purpose of this study was to test the following interrelated hypotheses in a larger sample by attempting to replicate supportive results from a small therapeutic study: (1) the pathogenesis of panic disorder includes at least two identifiable components: a biological component represented by spontaneous (unexpected) panic attacks, and a cognitive component represented by situational attacks and especially by phobias; (2) these components respond differently to treatment; (3) many biological processes respond to an effective intervention in proportion to their deviance from "normal" prior to treatment ("Law of Initial Value"); and (4) the response of spontaneous panic attacks to an effective treatment conforms to that model. Previously, the authors reanalyzed an 8-week therapeutic study of panic disorder that included groups treated with placebo and with imipramine (225 mg daily). The criteria of response were spontaneous panic attacks (biological component), situational panic attacks (both components), and agoraphobia ratings (cognitive component). The analyses compared the regression lines for posttreatment status on pretreatment status in the imipramine and placebo groups. The effect of imipramine on spontaneous panic attacks fitted the hypothesized model: the pre-post slope in the placebo group was approximately 1 (45 degrees), whereas the slope in the imipramine group was approximately 0. There was no significant difference in pre-post slopes between the imipramine and placebo groups for situational panic attacks or agoraphobia ratings. For this report, the authors applied the same approach to another larger data set from a study using a similar design, but a different antidepressant. In this multicenter, double-blind study, patients with panic disorder were randomly assigned to receive 10 weeks of treatment with placebo (N = 78) or fluoxetine 10 mg (N = 84) or 20 mg (N = 81) daily. Spontaneous and situational panic attacks were registered in a daily diary, and agoraphobia was rated at each visit. Using baseline and endpoint data, fluoxetine had a statistically significant, dose-dependent, suppressive effect on spontaneous panic attacks, as measured by the pre-post slopes in the three treatment groups. The placebo group showed some response (slope = 0.69). There were no significant drug effects on situational panic attacks. On ratings of agoraphobia, the slopes in the placebo and the fluoxetine 20 mg groups did not differ, but the slope in the fluoxetine 10 mg group was significantly less than that in the placebo group, suggesting a therapeutic drug effect on agoraphobia only at the lower dose. These results are consistent with the stated hypotheses. They suggest that the therapeutic effects of antidepressants on panic disorder may be due primarily to the specific suppression of spontaneous panic attacks among patients with high baseline pathologic findings. Implications of these results for concepts of pathogenesis, clinical practice, and therapeutic research regarding panic disorder are discussed.     

Fluoxetine treatment of depressed patients with comorbid anxiety disorders

Major depression with comorbid anxiety disorder is associated with poor antidepressant outcome compared to major depression without comorbid anxiety disorder. The purpose of our study was to assess changes in severity of both depressive and anxiety symptoms in outpatients with major depression with comorbid anxiety disorder following fluoxetine treatment. We enrolled 123 outpatients (mean age 38.9 +/- 10.8 years; 49% women) with major depressive disorder accompanied by one or more current comorbid anxiety disorders in our study. Patients were treated openly with fluoxetine 20 mg/day for 8 weeks. Efficacy assessments included the 17-item Hamilton Rating Scale for Depression (HAM-D) and the patient-rated Symptom Questionnaire (SQ) Scales for Depression and Anxiety. The mood and anxiety disorder modules of the Structured Clinical Interview for DSM-III-R were administered at screen and endpoint. We used 'intent-to-treat' analysis in examining all patients assigned to treatment and completing the baseline visit. The mean number of comorbid anxiety disorders per patient was 1.5 +/- 0.68. The mean HAM-D-17 score and mean Clinical Global Impressions-Severity scores decreased significantly from baseline to endpoint (week 8) following fluoxetine treatment (p < 0.0001). There were significant decreases in all four SQ scale scores, from baseline to endpoint: depression, anxiety, somatic symptoms and anger-hostility (p < 0.0001). Fifty-three percent of patients (n = 65) were depression responders (i.e. > or = 50% decrease in HAM-D-17 score at endpoint) and 46% (n = 57) were remitters (HAM-D-17 < or = 7 at endpoint). Patients with panic disorder had significantly higher baseline HAM-D-17 scores compared to those without panic disorder (p < 0.01). Patients with comorbid obsessive-compulsive disorder (OCD) were significantly less likely to be responders to fluoxetine at endpoint (> or = 50% decrease in HAM-D-17) and to be remitters (HAM-D-17 score of s 7 at endpoint) compared to patients without comorbid OCD (p < 0.01). Of the 41 patients on whom endpoint Structured Clinical Interview for DSM-III-R modules for anxiety disorders were available, 49% (n = 20) no longer met criteria for one or more of their anxiety disorder diagnoses at endpoint. Our preliminary findings suggest that fluoxetine is effective in treating outpatients with major depression with comorbid anxiety disorders, with a significant effect on both depression and anxiety symptoms. Further double-blind, placebo-controlled trials are required in larger samples to confirm our findings.     

A randomized, naturalistic, parallel-group study for the long-term treatment of panic disorder with clonazepam or paroxetine

This long-term extension of an 8-week randomized, naturalistic study in patients with panic disorder with or without agoraphobia compared the efficacy and safety of clonazepam (n = 47) and paroxetine (n = 37) over a 3-year total treatment duration. Target doses for all patients were 2 mg/d clonazepam and 40 mg/d paroxetine (both taken at bedtime). This study reports data from the long-term period (34 months), following the initial 8-week treatment phase. Thus, total treatment duration was 36 months. Patients with a good primary outcome during acute treatment continued monotherapy with clonazepam or paroxetine, but patients with partial primary treatment success were switched to the combination therapy. At initiation of the long-term study, the mean doses of clonazepam and paroxetine were 1.9 (SD, 0.30) and 38.4 (SD, 3.74) mg/d, respectively. These doses were maintained until month 36 (clonazepam 1.9 [SD, 0.29] mg/d and paroxetine 38.2 [SD, 3.87] mg/d). Long-term treatment with clonazepam led to a small but significantly better Clinical Global Impression (CGI)-Improvement rating than treatment with paroxetine (mean difference: CGI-Severity scale -3.48 vs -3.24, respectively, P = 0.02; CGI-Improvement scale 1.06 vs 1.11, respectively, P = 0.04). Both treatments similarly reduced the number of panic attacks and severity of anxiety. Patients treated with clonazepam had significantly fewer adverse events than those treated with paroxetine (28.9% vs 70.6%, P < 0.001). The efficacy of clonazepam and paroxetine for the treatment of panic disorder was maintained over the long-term course. There was a significant advantage with clonazepam over paroxetine with respect to the frequency and nature of adverse events.     

Short‐term and long‐term evaluation of selective serotonin reuptake inhibitors in the treatment of panic disorder: fluoxetine vs citalopram

This double‐blind study evaluates the efficacy and tolerability of fluoxetine and citalopram in the acute and long‐term treatment of panic disorder in 42 patients meeting DSM‐IV criteria for panic disorder with or without agoraphobia. Fluoxetine and citalopram showed similar efficacy in the treatment of panic disorder patients. On the basis of HRSA and PASS mean score evaluation, fluoxetine was more rapid than citalopram in reducing generalized anxiety symptoms, spontaneous panic attacks and anticipatory anxiety. Fluoxetine appeared to be effective at a dosage of 10 mg/day, while citalopram reached the same efficacy at a dosage of 30 mg/day. Long‐term evaluation has demonstrated high rates of persistent full remission with both drugs. Copyright © 1999 John Wiley & Sons, Ltd.     

A comparison of trazodone and fluoxetine: implications for a serotonergic mechanis of antidepressant action

Trazodone is an atypical antidepressant drug that is commonly referred to as a serotonin (5-hydroxytryptamine; 5-HT) uptake inhibitor. However, the most potent pharmacological effect of trazodone appears to be antagonist action at 5-HT_2/1C receptors. This is in contrast to fluoxetine, for which inhibition of 5-HT uptake is the most potent pharmacological action. The effects of trazodone and fluoxetine on several antidepressant drug screens are mediated by antagonist action at 5-HT₂ receptors and inhibition of 5-HT uptake, respectively. While fluoxetine is an effective agent for the treatment of major depression, obsessive-compulsive disorder (OCD) and panic disorder, trazodone does not appear to be effective in the treatment of OCD and panic disorder. In addition, trazodone and fluoxetine differ in humans with respect to their effects on sleep and weight. Taken together, the preclinical and clinical data suggest that trazodone acts as an antidepressant via antagonist action at 5-HT_2/1C receptors, while fluoxetine likely acts as an antidepressant via inhibition of 5-HT uptake.     

米氮平与氟西汀治疗抑郁症的多中心对照研究

目的 :评价米氮平与氟西汀治疗抑郁症的有效性和安全性。方法 :采用DSM Ⅳ抑郁症的诊断标准 ,为期 6wk的观察。结果 :经 6wk治疗 ,米氮平组有效率和治愈率分别为 78%和 64% ,氟西汀组为 90 %和 55% (P >0 .0 5)。治疗 1wk后 ,米氮平组的有效率高于氟西汀组。 2组HAMD和MADRS总分治疗前后比较差异有显著意义 ,2组间差异无显著意义。治疗 1wk后 ,米氮平组HAMD总分和睡眠紊乱因子分的减分较氟西汀组明显。米氮平组主要不良反应是眩晕或 (和 )头昏等 ,与氟西汀组相比 ,米氮平组嗜睡发生率高 (P <0 .0 5)。结论 :米氮平是一种安全、有效的新型抗抑郁药物。起效较快 ,且有改善焦虑及睡眠作用     

Panic disorder. A long‐term treatment study: fluoxetine vs imipramine

This double‐blind study evaluates the efficacy and tolerability of fluoxetine and imipramine in the acute and long‐term treatment of panic disorder in 38 patients meeting DSM‐IV criteria for panic disorder with or without agoraphobia. On the basis of HRSA mean scores evaluation, fluoxetine was found to be quicker than imipramine in reducing generalized anxiety at the end of the first week of treatment. However, through PASS and CGI mean scores evaluation, no statistically significant differences were found at any time in the efficacy of fluoxetine and imipramine on the total number of panic attacks, anticipatory anxiety or phobia severity. Fluoxetine has also turned out to be better tolerated than imipramine and to be effective at dosages low enough to avoid the event of an activation syndrome. Long‐term evaluation has shown high rates of persistent remission with both drugs. Copyright © 1999 John Wiley & Sons, Ltd.     

Fluoxetine--do the benefits outweigh the risks in adolescent major depression?

Major depressive disorder probably occurs in approximately 5% of adolescents. In these adolescents, selective serotonin re-uptake inhibitors (SSRIs), other than fluoxetine, have shown limited benefit and may increase the risk of suicide. In the Treatment for Adolescents with Depression Study, treatment with fluoxetine of adolescents diagnosed with major depressive disorder, or with the combination of fluoxetine and cognitive behavioural therapy, was superior to placebo. Cognitive behavioural therapy alone was not shown to be superior to placebo. Of the patients in the study, 27% had at least minimal suicidal ideation at baseline, and this reduced to 9% at the end of the treatment period, with the reduction being similar in each of the treatment groups. There were more suicide-related adverse events in the patients treated with fluoxetine (15 of 216) than in patients not treated with fluoxetine (9 of 223). There were no actual suicides. Although further investigation of any association between fluoxetine and suicidal tendencies is clearly required, at present, fluoxetine is the only SSRI for which benefit has been clearly shown, and the benefits seem to outweigh the risks. Thus, fluoxetine should generally be the first choice drug of clinicians if they decide that antidepressant drug treatment is indicated in adolescents with major depressive disorder.     

Fluoxetine – do the benefits outweigh the risks in adolescent major depression?

Major depressive disorder probably occurs in ～ 5% of adolescents. In these adolescents, selective serotonin re-uptake inhibitors (SSRIs), other than fluoxetine, have shown limited benefit and may increase the risk of suicide. In the Treatment for Adolescents with Depression Study, treatment with fluoxetine of adolescents diagnosed with major depressive disorder, or with the combination of fluoxetine and cognitive behavioural therapy, was superior to placebo. Cognitive behavioural therapy alone was not shown to be superior to placebo. Of the patients in the study, 27% had at least minimal suicidal ideation at baseline, and this reduced to 9% at the end of the treatment period, with the reduction being similar in each of the treatment groups. There were more suicide-related adverse events in the patients treated with fluoxetine (15 of 216) than in patients not treated with fluoxetine (9 of 223). There were no actual suicides. Although further investigation of any association between fluoxetine and suicidal tendencies is clearly required, at present, fluoxetine is the only SSRI for which benefit has been clearly shown, and the benefits seem to outweigh the risks. Thus, fluoxetine should generally be the first choice drug of clinicians if they decide that antidepressant drug treatment is indicated in adolescents with major depressive disorder.     

Pentagastrin induced panic attacks: enhanced sensitivity in panic disorder patients

The effects of pentagastrin, a synthetic analogue of the cholecystokinin tetrapeptide (CCK₄), were studied in 15 patients with panic disorder and 15 healthy controls. Three different intravenous dosages of pentagastrin (0.1, 0.3 and 0.6 µg/kg) and saline were investigated. Subjects were randomly allocated to two of the four treatment groups and tested on two separate occasions, 1 week apart, using an unbalanced double-blind incomplete block design. The mean panic rate with pentagastrin was 55% (12/22) for patients and 5% (1/22) for controls. None of the subjects panicked with saline. The frequency of panic attacks between the three pentagastrin doses in patients was not different. One control subject had a panic-like attack at the highest dose of pentagastrin. These findings concur with previous studies on the panicogenic effect of CCK₄ and pentagastrin and suggest a greater sensitivity for CCK receptor agonists in patients suffering from panic disorder than in healthy controls.     

Effect of acute and chronic benzodiazepines on plasma GABA in anxious patients and controls

The acute effects of diazepam on plasma GABA were determined in 18 patients with panic disorder, 13 patients with generalized anxiety disorder and 20 healthy controls. All subjects were benzodiazepine-naive. Four logarithmically increasing doses of diazepam/placebo were administered intravenously at 15-min intervals on 2 separate days. Plasma GABA was measured at baseline and 3 min after the highest dose of diazepam/placebo. There was an overall decrease in plasma GABA that was significantly greater following diazepam compared with placebo, but no group differences in response. In a separate group of 18 panic disorder patients receiving chronic benzodiazepine treatment with alprazolam, the same diazepam infusion procedure (no placebo day) produced decreases in plasma GABA similar to those seen in the untreated panic disorder patients. The clinical and physiologic implications of these findings are discussed.     

A double-blind, randomized, controlled trial of fluoxetine plus quetiapine or clomipramine versus fluoxetine plus placebo for obsessive-compulsive disorder

Obsessive-compulsive disorder patients who do not improve sufficiently after treatment with a selective serotonin reuptake inhibitor might improve further if other drugs were added to the treatment regimen. The authors present a double-blind, placebo-controlled trial comparing the efficacy of adding quetiapine or clomipramine to a treatment regimen consisting of fluoxetine. Between May 2007 and March 2010, a total of 54 patients with a primary diagnosis of obsessive-compulsive disorder, as defined by Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, Text Revision, and a current Yale-Brown Obsessive-Compulsive Scale (Y-BOCS) score of at least 16, the score having dropped by less than 35% after fluoxetine monotherapy, were allocated to 1 of 3 arms (n = 18 per arm): quetiapine + fluoxetine (≤200 and ≤40 mg/d, respectively), clomipramine + fluoxetine (≤75 and ≤40 mg/d, respectively), or placebo + fluoxetine (≤80 mg/d of fluoxetine). Follow-up was 12 weeks. The Y-BOCS scores were the main outcome measure. No severe adverse events occurred during the trial, and 40 patients (74%) completed the 12-week protocol. The Y-BOCS scores (mean [SD]) were significantly better in the placebo + fluoxetine and clomipramine + fluoxetine groups than in the quetiapine + fluoxetine group (final: 18 [7] and 18 [7], respectively, vs 25 [6], P < 0.001) (reduction from baseline: -6.7 [confidence interval {CI}, -9.6 to -3.8; and -6.5 [CI, -9.0 to -3.9], respectively, vs -0.1 [CI, -2.9 to 2.7], P < 0.001; number needed to treat = 2.4). The clomipramine-fluoxetine combination is a safe and effective treatment for fluoxetine nonresponders, especially those who cannot tolerate high doses of fluoxetine. However, the period of monotherapy with the maximum dose of fluoxetine should be extended before a combination treatment strategy is applied.     

The efficacy of sertraline in panic disorder: combined results from two fixed-dose studies

Data from two fixed-dose studies of sertraline in panic disorder were pooled in order to provide sufficient power for the analysis of treatment response in clinically relevant subgroups. Male and non-fertile female patients meeting DSM-III-R criteria for moderate-to-severe panic disorder with or without agoraphobia completed a 1-2 week placebo run-in period, and then were randomized to 12 weeks of double-blind treatment with either placebo, or one of three fixed daily doses of sertraline (50 mg, 100 mg, or 200 mg). Eighty-two patients were treated with placebo and 240 patients were treated with one of three doses of sertraline. All three sertraline doses produced significant efficacy compared to placebo, with no consistent evidence of a dose-response effect. For the subset of patients with subsyndromic depression at baseline [baseline Hamilton Depression Rating scale (HAM-D > 12 and < or = 21], sertraline yielded a significantly higher panic-free rate than did placebo (P = 0.021), again, by a conservative endpoint (Last Observation Carried Forward method, LOCF) analysis. Sertraline was well-tolerated at all dose levels, with no significant between-dose differences in patients discontinuing due to adverse events. The presence of mild-to-moderate subsyndromic levels of depression did not reduce the anti-panic efficacy of sertraline.     

Interactive model of therapeutic response in panic disorder: moclobemide,a case in point

It was proposed that pre-post regression slopes be used to index treatment response when the effect of baseline scores differed among treatments (interaction between treatment and baseline score). Reanalyses of two studies using imipramine and fluoxetine in panic disorder showed doserelated decreases in pre-post slopes for the frequency of unexpected panic attacks, but not for the frequency of situational panic attacks or measures of agoraphobia. This report presents similar analyses of data from a study using moclobemide. Patients (N = 452) with panic disorder were randomized to placebo or a fixed dose of moclobemide (75, 150, 300, 600, or 900 mg/day). They were treated double-blindly and evaluated at baseline and 1, 2, 3, 4, 6, and 8 weeks later. The authors analyzed the frequency of unexpected and situational panic attacks compiled from a daily diary, and fear and avoidance ratings based on the patient's main phobia using baseline (pre) and end-point (post) values for all randomized patients. Adjoining dose groups were combined. Both unexpected and situational panic attacks showed systematic doserelated suppression of pre-post treatment slopes. Neither pre-post slopes nor adjusted posttreatment means for fear and avoidance differed reliably between treatment arms. This study replicates the authors' earlier findings, except for situational panic attacks, which probably were not reliably identified. Antidepressants selectively suppress panic attacks, especially unexpected attacks, but not agoraphobia. The findings are consistent with the hypothesis that panic disorder with agoraphobia has clinically separable biologic and cognitive components that respond differentially to treatment. Antidepressants benefit primarily patients with many unexpected panic attacks. Investigators should evaluate pre-post treatment slopes before comparing adjusted posttreatment means (analysis of covariance).     

Treatment of adolescent obsessive-compulsive disorder with a clomipramine-fluoxetine combination

Clomipramine has been reported to be effective in the treatment of obsessive-compulsive disorder (OCD). Children and adolescents, however, tolerate poorly the adverse effects of tricyclics. Fluoxetine and other serotonin re-uptake inhibitors also appear useful in OCD, and are safer than clomipramine. To maximize the therapeutic effects and minimize adverse effects, 6 adolescents with OCD were treated in single trials with a clomipramine-fluoxetine combination. Duration of combined drug therapy ranged from 4 weeks to more than 28 weeks. Patients were first treated with clomipramine alone; if improvement or adverse effects were unsatisfactory, they received the drug combination. Clinical global improvement with clomipramine alone was moderate in 3 patients and minimal in 3. With a combined clomipramine-fluoxetine therapy, improvements were marked in 5 patients, and moderate in 1. These improvements were obtained with relatively low daily doses: clomipramine at 25 to 50 mg, and fluoxetine at 20 to 40 mg. Adverse effects appeared greater and much less tolerable with clomipramine alone than with the clomipramine-fluoxetine combination. This drug combination was well tolerated. These preliminary data suggest that relatively low doses of a clomipramine-fluoxetine combination may potentiate therapeutic effects and minimize adverse effects in OCD patients. Larger controlled trials are suggested.     

Are patients who are intolerant to one SSRI intolerant to another?

One hundred patients with major depression who had discontinued fluoxetine because of side effects were enrolled in a multicenter, open, 8-week study of sertraline. After a washout period of at least 3 weeks following fluoxetine discontinuation and an additional 1-week, single-blind, placebo washout period, patients began treatment with 50 mg sertraline once daily. Based on the clinician's judgment of patient response, doses were titrated upward if necessary. The maximum daily dose of sertraline was 200 mg. Depressive symptoms and adverse events were assessed weekly. An interim analysis was conducted of the first 93 patients who completed the study. Of 91 evaluable patients, 69 sertraline-treated patients (75.8%) experienced significant improvement in depression. Only 8 of 93 patients (8.6%) discontinued sertraline because of side effects.     

文拉法辛缓释剂和帕罗西汀治疗惊恐障碍的随机对照研究

目的:比较文拉法辛缓释剂和帕罗西汀治疗惊恐障碍的有效性和安全性。方法:将73例符合CCMD-3R的惊恐障碍病人随机分为2组,分别给予文拉法辛(38例,初始剂量75 mg·d~(-1))和帕罗西汀(35例,初始剂量10 mg·d~(-1))。采用惊恐症状评定量表(PASS)、汉密尔顿焦虑量表(HAMA)、临床总体印象量表(CGI)和不良反应量表(TESS)分别在治疗前,治疗后wk 2、4、8末各评定1次,并进行对比分析。结果:2组间在治疗后wk 2、4末PASS、HAMA、CGI评分有显著差异(P<0.05);在wk 8末2组间差异无显著意义(P>0.05);文拉法辛组PASS、HAMA、CGI评分在治疗后wk 2末比治疗前明显降低(P<0.05),在wk 4、8末有进一步改善(P<0.01);帕罗西汀组PASS、HAMA、CGI评分在治疗后wk 4、8末与治疗前相比均降分明显(P<0.01)。2组不良反应发生率无显著差异。结论:文拉法辛是一种快速有效且安全性较高的治疗惊恐障碍的药物。     

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.