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At least 19 recordsLinked to original sources

PubMed2002

[Adverse effects after switching to a different generic form of paroxetine: paroxetine mesylate instead of paroxetine HCl hemihydrate].

Two patients, a 29-year-old man and a 32-year-old woman who were being treated with paroxetine HCl hemihydrate for depression and panic disorder with agoraphobia, respectively, unexpectedly developed complaints after switching to paroxetine mesylate. The symptoms were generalised itching with relapse of the depressive disorder in the man, and nausea with diarrhoea in the woman. The symptoms disappeared after the original treatment with paroxetine HCl hemihydrate was resumed. In the first patient, a rechallenge with the mesylate form of paroxetine led to the same complaints which subsided again after using the first product. Those treating such patients, and the patients themselves, should be informed if the delivery form of paroxetine is changed.

Adult↗

PubMed2005

Adherence to paroxetine CR compared with paroxetine IR in a Medicare-eligible population with anxiety disorders.

There are many challenges in the pharmacologic management of elderly patients with anxiety disorders, including an increased sensitivity to drug effects, reduced drug metabolism, and socioeconomic barriers leading to poor medication adherence. As such, the purpose of this study was to evaluate differential rates of adherence between paroxetine controlled release (CR) and paroxetine immediate release (IR) in the treatment of anxiety disorders in a Medicare-eligible population. Patients aged 65 years or older initiating therapy with paroxetine CR or paroxetine IR with a diagnosis of anxiety were identified from the Integrated Healthcare Information Services National Managed Care Benchmark database from July 2001 to February 2004. Logistic regression models were used to assess differences in 6-month adherence rates, controlling for differences in multiple background characteristics. Adherence was defined as having a minimum medication possession ratio of 80% over 180 days without evidence of a 15-day gap before 90 days of therapy. Of the 604 patients included in the study, 18% received paroxetine CR and 82% received paroxetine IR; comorbid anxiety and depression were present in 37.3% of patients. Overall, only 37.3% of patients adhered to therapy, with a greater percentage of patients adhering to paroxetine CR (45.0%) compared with paroxetine IR (35.6%). After controlling for background characteristics, patients receiving paroxetine IR were 38.7% less likely to adhere to therapy compared with patients receiving paroxetine CR (P = .0328). When stratified by those with comorbid anxiety and depression, patients receiving paroxetine IR were 55.1% less likely to adhere to therapy compared with patients receiving paroxetine CR (P = .0292). This study demonstrates that antidepressant nonadherence is common in patients older than 65 years of age, with overall rates of nonadherence at 62.7% and patients receiving paroxetine IR having the lowest levels of adherence. Future work should assess differences in all available selective serotonin reuptake inhibitors while also directly assessing the economic impact of nonadherence in the elderly population.

Aged↗

PubMed2003

Paroxetine-induced increase in metabolic end products of nitric oxide.

Decreased production of endothelium-derived nitric oxide has been implicated in the pathogenesis of cardiovascular diseases. Metabolic end products of nitric oxide (NO(x)) are often used as markers for endothelial nitric oxide production in humans. Decreased endothelium-derived nitric oxide has been suggested to mediate some of the deleterious effects of conventional cardiovascular risk factors such as hypercholesterolemia, smoking, and physical inactivity. A substantial number of patients with cardiovascular diseases suffer from comorbid major depressive disorder, which is a predictor of a poorer cardiovascular outcome. Paroxetine is a first-line antidepressant and has been reported to decrease plasma NO(x), theoretically suggesting a potential deleterious effect on the cardiovascular system. We assessed the hypothesis that paroxetine would induce a decrease in plasma NO(x) in healthy volunteers. Plasma NO(x) levels were measured by chemiluminescence at baseline, after 8 weeks of paroxetine administration, and at postdiscontinuation. Contrary to our hypothesis, we found that paroxetine administration induced a significant increase in NO(x) that normalized after paroxetine discontinuation. It remains to be demonstrated that the paroxetine-induced increase in NO(x) is associated with a modification of the cardiovascular risk in patients with major depressive disorder.

Adult↗

PubMed1997

A double-blind, multicenter study in primary care comparing paroxetine and clomipramine in patients with depression and associated anxiety. Paroxetine Study Group.

BACKGROUND: 60%-90% of patients with a primary diagnosis of depression also experience symptoms of anxiety, and such patients have a poorer prognosis than those with uncomplicated depression. The serotonin selective reuptake inhibitors have demonstrated efficacy in the treatment of both depression and certain anxiety states. Furthermore, in a metaanalysis of the paroxetine clinical trial database of 2963 patients in whom depression predominated, there was a concomitant reduction in the Hamilton Rating Scale for Depression anxiety factor. The purpose of the present study was to prospectively compare the efficacy of paroxetine and clomipramine in patients specifically selected for coexisting depression and anxiety. METHOD: This was a 12-week, double-blind, parallel-group trial comparing paroxetine 20-40 mg/day with clomipramine 75-150 mg/day in 1002 patients with a Montgomery-Asberg Depression Rating Scale (MADRS) score > or = 20 and a Clinical Anxiety Score (CAS) > or = 11 after a 3-7 day placebo run-in period. RESULTS: Both paroxetine and clomipramine reduced the MADRS and CAS ratings at 2, 6, and 12 weeks and at endpoint, with no significant differences between treatment groups at any time point. CGI severity of illness and global improvement ratings were also similar throughout the trial; however, there was a statistically significant difference in the CGI efficacy index at 6 weeks and at endpoint, favoring paroxetine (p = .015 and p = .015, respectively). Paroxetine resulted in fewer treatment-emergent adverse experiences and related withdrawals than clomipramine (p = .025 and p = .008, respectively). The number of serious adverse experiences was not significantly different in the paroxetine group compared with the clomipramine group (14 [2.8%] vs. 27 [5.4%]), but did approach statistical significance (p = .056). Anticholinergic-emergent adverse experiences were reported twice as frequently by patients in the clomipramine group as in the paroxetine group (36.1% vs. 18.6%). CONCLUSION: There was no evidence of any significant difference in efficacy between paroxetine and clomipramine in patients with coexisting depression and anxiety. However, paroxetine was better tolerated as shown by total treatment-emergent adverse experiences, anticholinergic adverse experiences, and withdrawals due to adverse experiences.

Adolescent↗

PubMed2006

Terbinafine increases the plasma concentration of paroxetine after a single oral administration of paroxetine in healthy subjects.

OBJECTIVE: Paroxetine is believed to be a substrate of CYP2D6. However, no information was available indicating drug interaction between paroxetine and inhibitors of CYP2D6. The aim of this study was to examine the effects of terbinafine, a potent inhibitor of CYP2D6, on pharmacokinetics of paroxetine. METHODS: Two 6-day courses of either a daily 150-mg of terbinafine or a placebo, with at least a 4-week washout period, were conducted. Twelve volunteers took a single oral 20-mg dose of paroxetine on day 6 of both courses. Plasma concentrations of paroxetine were monitored up to 48 h after dosing. RESULTS: Compared with the placebo, terbinafine treatment significantly increased the peak plasma concentration (C(max)) of paroxetine, by 1.9-fold (6.4 +/- 2.4 versus 12.1 +/- 2.9 ng/ml, p < 0.001), and the area under the plasma concentration-time curve from zero to 48 h [AUC (0-48)] of paroxetine by 2.5-fold (127 +/- 67 vs 318 +/- 102 ng/ml, p < 0.001). Elimination half-life differed significantly (15.3 +/- 2.4 vs 22.7 +/- 8.8 h, p < 0.05), although the magnitude of alteration (1.4-fold) was smaller than C(max )or AUC. CONCLUSION: The present study demonstrated that the metabolism of paroxetine after a single oral dose was inhibited by terbinafine, suggesting that inhibition of CYP2D6 activity may lead to a change in the pharmacokinetics of paroxetine. However, further study is required to confirm this phenomenon at steady state.

Administration, Oral↗

PubMed1997

Long-term evaluation of paroxetine, clomipramine and placebo in panic disorder. Collaborative Paroxetine Panic Study Investigators.

Paroxetine has been shown to be effective in panic disorder in three 10- to 12-week studies. This trial studied the longer term effects of paroxetine in patients with DSM-III-R defined panic disorder. Patients who satisfactorily completed a 12-week, double-blind, placebo-controlled study of paroxetine and clomipramine could choose to continue receiving their randomized treatment for a further 36 weeks. Efficacy assessments included the daily panic attack diary, the Clinical Global Impression Scale, the Hamilton Anxiety Rating Scale, the Marks Sheehan Phobia Scale and the Sheehan Disability Scale. In total, 176 patients were included in the intention-to-treat population. The number of full panic attacks decreased in all three groups during the 12-week study, and improvements continued with long-term therapy. Paroxetine was statistically significantly more effective than placebo throughout the long-term study with respect to reduction from baseline of full panic attacks, and at the end of treatment with respect to the proportion of patients who eventually experienced no panic attacks. There were no significant differences between paroxetine and clomipramine. The proportion of patients who withdrew from the study due to adverse effects was greater in the clomipramine group (19%) than in either the paroxetine group (7%) or the placebo group (9%). Paroxetine was significantly more effective than placebo and as effective as (but better tolerated than) clomipramine in the long-term treatment of panic disorder. Not only was efficacy maintained, but continued improvement was also seen, indicating the importance of long-term treatment in patients with panic disorder.

Adolescent↗

PubMed2003

Pharmacokinetics, drug interactions, and tolerability of paroxetine and paroxetine CR.

The development of paroxetine hydrochloride began in the late 1970s. An abundance of data have been accumulated from clinical investigations demonstrating the efficacy of paroxetine in the treatment of major depression and anxiety disorders. The published literature contains a substantial amount of supportive data documenting the safety, tolerability, and pharmacokinetic and pharmacodynamic properties of paroxetine. The role of paroxetine in clinically significant drug-drug interactions, especially involving metabolic inhibitory effects on the substrates of cytochrome p450 2D6, has long been suspected, but only isolated cases provide any evidence. Published data for widespread patient morbidity from drug interactions with paroxetine are almost nonexistent. Considerations of the pharmacokinetic properties of paroxetine support a rationale for the development of new dosage forms that maintain the efficacy yet improve the tolerability profile of the selective serotonin reuptake inhibitors. Paroxetine controlled-release is an enteric-coated formulation with release features that may enhance clinical outcome by modifying absorption-related pharmacokinetics, improving tolerability, and maintaining therapeutic benefits

Aged↗

PubMed1997

A comparison of paroxetine, clomipramine and placebo in the treatment of panic disorder. Collaborative Paroxetine Panic Study Investigators.

The aim of this 12-week, double-blind, parallel group, placebo-controlled study was to compare paroxetine with clomipramine in 367 patients with DSM-III-R defined panic disorder. Efficacy assessments included the daily panic attack diary, the Clinical Global Impression Scale, the Hamilton Anxiety Rating Scale, the Marks Sheehan Phobia Scale and the Sheehan Disability Scale. Paroxetine produced significant improvements compared with placebo in various measurements of panic attack frequency, and was as effective as clomipramine. However, paroxetine appeared to have a more rapid onset of action than clomipramine in reducing the number of panic attacks to zero. There was an equivalent improvement with both paroxetine and clomipramine in the supportive efficacy variables which assessed associated aspects of therapeutic improvement. Significantly more adverse effects were reported in the clomipramine group compared with the paroxetine group, while there was no difference between the paroxetine and placebo groups.

Adolescent↗

PubMed1999

Accelerating antidepressant response in geriatric depression: a post hoc comparison of combined sleep deprivation and paroxetine versus monotherapy with paroxetine, nortriptyline, or placebo.

Speed of response is an important clinical issue in the treatment of depressed elderly patients. Our objective was to compare rapid response rates in a study combining therapeutic sleep deprivation (TSD) with paroxetine with two earlier randomized, double-blind studies in late-life depression, one of paroxetine versus nortriptyline and another of nortriptyline versus placebo. We measured depressive symptoms with the 17-item Hamilton Rating Scale of Depression (HRSD), defining rapid response as an HRSD < or = 10 by 2 weeks. With combination therapy (TSD + paroxetine), 9 of 13 patients (69%) experienced a rapid response. In the nortriptyline versus paroxetine study, nortriptyline brought about rapid response in 12 of 37 (32%) and paroxetine in 11 of 43 patients (26%). In the third study, rapid response to nortriptyline occurred in 10 of 41 patients (24%) and to placebo in 6 of 39 patients (15%). The overall chi square, including the rate of rapid response to placebo, was 14.87 (P = .005). The chi square on the four active treatment groups, excluding placebo, was 10.28 (P = .016). This preliminary observation suggests that combined therapy with TSD plus paroxetine may be twice as successful at achieving rapid response in elderly depressed patients than conventional monotherapy with medication or placebo. A prospective, placebo-controlled evaluation of this dual therapy is warranted.

Aged↗

PubMed1999

Paroxetine in social phobia/social anxiety disorder. Randomised, double-blind, placebo-controlled study. Paroxetine Study Group.

BACKGROUND: Preliminary studies have suggested that paroxetine may be effective in social phobia/social anxiety disorder. AIMS: To assess the efficacy and tolerability of paroxetine in the acute (12-week) treatment of social phobia. METHOD: Two-hundred and ninety patients with social phobia were assigned randomly to paroxetine (20-50 mg/day flexible dose) or placebo for 12 weeks of double-blind treatment. Primary efficacy outcomes were the Liebowitz Social Anxiety Scale (LSAS) total score (patient-rated) and the Clinical Global Impression (CGI) scale global improvement item. The secondary efficacy variables included CGI scale severity of illness score and the patient-rated Social Avoidance and Distress Scale. RESULTS: Paroxetine produced a significantly greater reduction in LSAS total score (mean change from baseline: -29.4 v. -15.6; P < or = 0.001) and a greater proportion of responders (score < or = 2 on CGI global improvement) (65.7% v. 32.4%; P < 0.001) compared with placebo at the end of the 12-week study period. Both primary efficacy variables were statistically significant compared with placebo from week 4 onwards. Paroxetine was generally well tolerated. CONCLUSIONS: Paroxetine is an effective, well-tolerated treatment for patients with social phobia.

Adolescent↗

PubMed2002

A prospective study comparing paroxetine alone versus paroxetine plus sildenafil in patients with premature ejaculation.

PURPOSE: We compared the efficacy of paroxetine alone and combined with sildenafil in patients complaining of premature ejaculation. MATERIALS AND METHODS: Enrolled in this study were 80 consecutive potent men 19 to 47 years old (mean age 34) with premature ejaculation but without any obvious organic cause. Pretreatment evaluation included a history, self-administration of the International Index of Erectile Function (IIEF) questionnaire, physical examination and the Meares-Stamey test to exclude genital tract infection. The initial 40 patients received 10 mg. paroxetine daily for 21 days and then 20 mg. as needed, that is 3 to 4 hours before planned sexual activity, for 6 months (group 1). The other group of 40 men received 10 mg. paroxetine daily for 21 days and then 20 mg. as needed plus 50 mg. sildenafil as needed, that is 1 hour before planned sexual activity, for 6 months (group 2). Patients were followed 3 and 6 months after beginning therapy and were evaluated using several general assessment questions, IIEF and ejaculatory latency time. RESULTS: Mean ejaculatory latency time +/- SE in group 1 was 0.33 +/- 0.04, 3.7 +/- 0.10 (p <0.01) and 4.2 +/- 0.03 (p <0.01) minutes at baseline, 3 and 6-month followup, while in group 2 it was 0.35 +/- 0.03, 4.5 +/- 0.07 (p <0.01) and 5.3 +/- 0.02 (p <0.001) minutes, respectively. When improvement in ejaculatory latency time was compared in the 2 groups, group 2 results proved to be significantly greater (p <0.05). Baseline, and 3 and 6-month mean intercourse satisfaction domain values of the IIEF were 9, 11 and 11 (p = 0.09, not significant), and 9, 11 and 14 (p <0.05) in groups 1 and 2, respectively. Group 2 patients reported significantly greater intercourse satisfaction than those in group 1 (p <0.05). At baseline, 3 and 6 months there was a mean of 0.9 +/- 0.1, 1.7 +/- 0.3 (not significant) and 2.5 +/- 0.3 (p <0.01) coitus episodes weekly in group 1, and 1 +/- 0.2, 2.3 +/- 0.3 (p <0.01) and 3.2 +/- 0.1 (p <0.001) in group 2, respectively. Group 2 patients reported a significantly higher number of coitus episodes weekly (p <0.05). Side effects in the 40 group 1 cases included anejaculation in 1 (2.5%), gastrointestinal upset and/or nausea in 5 (12.5%), headache in 4 (10%) and decreased libido in 2 (5%). Side effects in the 40 group 2 cases included anejaculation in 1 (2.5%), headache in 8 (20%), gastrointestinal upset and/or nausea in 6 (15%) and flushing in 6 (15%). Group 2 patients reported significantly more headaches (p <0.01) and flushing episodes (p <0.001) than those in group 1. After 6 months of treatment 33 men (82.5%) in group 1 and 36 (90%) in group 2 were willing to continue therapy (not significant). CONCLUSIONS: Paroxetine combined with sildenafil appears to provide significantly better results in terms of ejaculatory latency time and intercourse satisfaction versus paroxetine alone in potent patients with premature ejaculation. However, combined treatment is associated with a mild increase in drug related side effects.

Adult↗

PubMed2002

A comparison of paroxetine versus paroxetine plus amisulpride in the treatment of dysthymic disorder: efficacy and psychosocial outcomes.

Dysthymic disorder is a chronic depressive condition with considerable psychosocial impairment. Even if DD patients respond to various antidepressant medications, there has been little systematic study on antidepressant-refractory DD. Only a few trials have evaluated the effects of treatment on psychosocial functioning of dysthymic patients. In this 3-month, open-label study, 60 outpatients with DSM-IV criteria for dysthymic disorder who failed to respond to 3-month treatment with paroxetine 20 mg/day were randomly assigned to treatment with paroxetine 40 mg/day or paroxetine 20 mg/day plus amisulpride 50 mg/day. The effects of the two treatments were assessed for both mood symptoms (21-item Hamilton Rating Scale for Depression, Montgomery-Asberg Depression Rating Scale, Clinical Global Impression, severity and improvement) and psychosocial outcomes (DSM-IV Global Assessment of Functioning, Social Adaptation Self-evaluation Scale). Analysis of variance on all rating scales showed that both treatments were effective over this observation period. Response and remission rates did not differ in the treatment groups. A significantly greater psychosocial improvement was observed in the group receiving combined treatment compared with patients receiving paroxetine alone. Both treatments appeared to be effective in our sample of dysthymic subjects. Combined treatment with paroxetine and amisulpride resulted in a better outcome in terms of social functioning.

Adult↗

PubMed1998

One year real world prospective follow-up study of a major depressive episode of patients treated with paroxetine and pindolol or paroxetine for 6 weeks.

The objective of our study was an assessment of outcome in a 1 year 'real world', prospective follow-up study of patients who were treated with paroxetine 20 mg plus pindolol 7.5 mg or paroxetine 20 mg plus placebo for 6 weeks. Eighty patients recruited to a double-blind placebo-controlled randomized 6 weeks study of paroxetine and pindolol were followed up for 6 months and interviewed after 1 year. A Kaplan-Meier survival analysis of the patients who relapsed having taken paroxetine and pindolol, compared with those who relapsed having taken paroxetine and placebo, shows that the pindolol group had a better clinical outcome. After 1 year patients who had responded to medication by 2 weeks had done better than the rest and they had been more compliant with medication for 6 months. There are indications that the earlier a patient responds to medication, the better the long-term outcome.

Adult↗

PubMed1996

Paroxetine versus clomipramine in the treatment of obsessive-compulsive disorder. OCD Paroxetine Study Investigators.

BACKGROUND: The aim was to assess the effect of a flexible dose of paroxetine, compared with clomipramine and placebo, in obsessive-compulsive disorder (OCD). METHOD: In a multinational randomised study, 406 subjects with OCD of at least six months duration received double-blind medication for up to 12 weeks. Doses were adjusted according to therapeutic effect and side-effects. Primary efficacy measures were the Yale-Brown Obsessive-Compulsive Scale and the National Institute of Mental Health Obsessive-Compulsive Scale. Secondary efficacy measures were the Montgomery-Asberg Depression Rating Scale, Symptom Check-List (90), Clinical Global Impression, and Patients Global Evaluation. RESULTS: Paroxetine was significantly more effective than placebo, and of comparable efficacy to clomipramine. Paroxetine had significantly superior tolerability to clomipramine on three measures: CGI efficacy index, anticholinergic adverse events, and adverse events leading to withdrawal. CONCLUSION: Paroxetine is as effective as clomipramine in the treatment of OCD. The comparable efficacy and better tolerability of paroxetine suggest that it would be an appropriate treatment for OCD.

Adolescent↗

PubMed1992

A double-blind multicentre study of paroxetine and amitriptyline in depressed outpatients. Italian Paroxetine Study Group.

A comparative double-blind study of paroxetine and amitriptyline in the treatment of depressed hospital outpatients was undertaken at 15 centres in Italy. Three hundred and nine patients of either sex were admitted to the study. The starting dose of paroxetine was 20 mg daily and of amitriptyline 75 mg daily in divided doses; at week 3 these doses could be increased at the investigators' discretion. Efficacy was measured on the Hamilton Depression Rating Scale and on Clinical Global Impression. Both treatment groups showed significant improvement at week 6 with no significant between-group differences. Significantly fewer patients receiving paroxetine reported adverse events compared with those on amitriptyline (44% vs 62%; p < 0.01 in favour of paroxetine).

Adult↗

PubMed2005

Neonatal symptoms following maternal paroxetine treatment: serotonin toxicity or paroxetine discontinuation syndrome?

We report a case of neonatal symptoms of irritability, increased tonus and convulsions after in-utero exposure to paroxetine 30 mg/day. The infant's symptoms commenced on the first day after birth and persisted for 10 days. Paroxetine levels were undetectable on day 6. Extensive investigations excluded infective and metabolic causes. Serotonin toxicity due to paroxetine seems the most likely mechanism, though an important differential diagnosis is a paroxetine discontinuation (withdrawal) syndrome. Differentiating between these two syndromes in the neonate presents a dilemma for clinicians. Irrespective of the mechanism, we recommend that all neonates exposed to antidepressants, particularly serotonin reuptake inhibitors (SSRIs), during the last trimester should be followed-up closely for adverse symptoms commencing in the first 10 days after birth. The possibility of such symptoms needs to be discussed with women who are considering starting or continuing antidepressant treatment in pregnancy. All neonatal adverse drug events should be reported to a pharmacovigilance centre. Further research is warranted.

Adult↗

PubMed2003

Combined paroxetine and clonazepam treatment strategies compared to paroxetine monotherapy for panic disorder.

Despite the widespread application of combined selective serotonin reuptake inhibitors (SSRI) and benzodiazepine treatment for panic disorder, there has been relatively little systematic assessment of the safety and efficacy of this therapeutic strategy. Although the limited number of studies to date suggest a more rapid onset of benefit with combined treatment, this study is the first to address the critical question of whether continued combined treatment confers superior efficacy. This study is a randomized, double-blind, three-arm study in patients with panic disorder (n = 60), comparing the efficacy and safety of paroxetine and placebo (PP), paroxetine coadministered with clonazepam followed by a tapered benzodiazepine discontinuation phase (PC-D), and ongoing combination treatment (PC-M). All treatment groups demonstrated significant improvement by endpoint. There was a significant advantage for the combined treatment groups early in treatment but, subsequently, outcome in all three groups was similar. A trend towards greater achievement of endpoint remission status for the PC-D group was attenuated when variability in baseline severity was considered. The results of this study should be interpreted in the context of a relatively moderate sample size and higher rates of early dropout. Combined treatment with paroxetine and clonazepam resulted in more rapid response than with the SSRI alone, but there was no differential benefit beyond the initial few weeks of therapy. Initiating combined treatment followed by benzodiazepine taper after a few weeks may provide early benefit while avoiding the potential adverse consequences of long-term combination therapy.

Adolescent↗

PubMed2004

Double-blind, placebo-controlled assessment of combined clonazepam with paroxetine compared with paroxetine monotherapy for generalized social anxiety disorder.

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.

Adult↗