Efficacy and safety of paroxetine treatment for chronic PTSD: a fixed-dose, placebo-controlled study.

OBJECTIVE: This study evaluated the efficacy and safety of paroxetine for the treatment of patients with chronic posttraumatic stress disorder (PTSD). METHOD: Outpatients with chronic PTSD according to DSM-IV criteria and a score of 50 or more on the Clinician-Administered PTSD Scale, part 2, were randomly assigned to take placebo (N=186), 20 mg/day of paroxetine (N=183), or 40 mg/day of paroxetine (N=182) for 12 weeks. Efficacy was assessed by examining the change in total score from baseline to endpoint on the Clinician-Administered PTSD Scale, part 2, and rates of response ("very much improved" or "much improved") for global improvement on the Clinical Global Impression scale. RESULTS: Paroxetine-treated patients in both dose groups demonstrated significantly greater improvement on primary outcome measures compared to placebo-treated patients in the intent-to-treat analysis. Moreover, paroxetine treatment resulted in statistically significant improvement compared to placebo on all three PTSD symptom clusters (reexperiencing, avoidance/numbing, and hyperarousal), social and occupational impairment, and comorbid depression. Paroxetine was effective for both men and women. Treatment response did not vary by trauma type, time since trauma, or severity of baseline PTSD or depressive symptoms. Both doses were well tolerated. CONCLUSIONS: Doses of 20 and 40 mg/day of paroxetine are effective and well tolerated in the treatment of adults with chronic PTSD.

Paroxetine in the treatment of generalized anxiety disorder: results of a placebo-controlled, flexible-dosage trial.

BACKGROUND: The objective of this randomized, double-blind, placebo-controlled study was to investigate the efficacy and safety of paroxetine in outpatients with generalized anxiety disorder (GAD). METHOD: Male and female outpatients 18 years and older who met DSM-IV criteria for GAD and had baseline scores of at least 20 on the Hamilton Rating Scale for Anxiety (HAM-A) were randomly assigned to treatment with paroxetine (20-50 mg/day) or placebo for 8 weeks. The primary efficacy variable was the mean change from baseline in the total score of the HAM-A. Additional key efficacy variables were the change from baseline in the scores of the HAM-A items anxious mood and tension, the anxiety subscale of the Hospital Anxiety and Depression Scale, and the Sheehan Disability Scale (SDS). The proportions of patients fulfilling response and remission criteria at week 8 were also determined. RESULTS: The intent-to-treat population included 324 patients. At week 8, compared with the placebo group (N = 163), the paroxetine group (N = 161) had a significantly greater reduction of GAD symptoms on all of the above-mentioned efficacy variables. On the HAM-A anxious mood item, which encompasses the cardinal symptoms of GAD, significantly greater efficacy was observed from week 1 and on the SDS significantly greater improvement was documented in the domain "social life" as early as week 4 for paroxetine compared with placebo. In both the last-observation-carried-forward and completer data sets, significantly greater proportions of paroxetine-treated patients achieved response or remission by week 8. Treatment with paroxetine was well tolerated, and the number and type of adverse events recorded in the paroxetine group correspond to the known safety profile of this medication. 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.

Changes in quantitatively assessed tremor during treatment of major depression with lithium augmented by paroxetine or amitriptyline.

Tremor is a relatively frequent side effect of lithium and of antidepressants with serotonergic properties. It can be expected that combinations of lithium (which is itself serotonergic) with such antidepressants will enhance not only efficacy, but also the incidence of side effects, including tremor. To quantitatively monitor the effect of antidepressant augmentation of ongoing lithium therapy on tremor, lithium-maintained patients with a breakthrough episode of major depression were randomly assigned under double-blind conditions to receive paroxetine 20 mg/day (N = 14) or amitriptyline 75 mg/day (N = 17). The initial dosages could be increased after 2 weeks to 40 mg/day and 150 mg/day, respectively, and the patients were treated for 6 weeks. Tremor activity was assessed weekly, quantitatively by accelerometry and qualitatively with the Dosage Record and Treatment Emergent Symptom Scale. Statistical analysis detected no significant difference between the treatment groups with respect to changes in mean tremor activity relative to baseline. However, analysis of the pooled data showed that tremor increased significantly during the course of combined lithium and antidepressant therapy, with the greatest increments occurring independent of dosage approximately 3 weeks after initiation of combination treatment. Although the mean tremor activity subsided toward the end of treatment, tremor activity on the whole was still significantly greater after 6 weeks of combined lithium and antidepressant treatment than at the start of combination therapy. Increased tremor was not associated with decreased medication compliance, and no patient discontinued treatment because of increased tremor. Tremor frequency was not affected by the study treatments.

Paroxetine in the treatment of chronic posttraumatic stress disorder: results of a placebo-controlled, flexible-dosage trial.

BACKGROUND: The objective of this double-blind, placebo-controlled study was to investigate the efficacy and safety of paroxetine in outpatients with posttraumatic stress disorder (PTSD). METHOD: Male and female outpatients 18 years and older who met DSM-IV criteria for PTSD and had baseline scores of 50 or greater on the Clinician Administered PTSD Scale (CAPS-2) were randomly assigned to treatment with paroxetine (20-50 mg/day) or placebo for 12 weeks. The primary efficacy variables were the change from baseline to the 12-week endpoint in the CAPS-2 total score and the proportion of responders on the Clinical Global Impressions-Global Improvement scale (CGI-1). Additional key outcome measures were the change from baseline in the reexperiencing, avoidance/ numbing, and hyperarousal scores of the CAPS-2 and in the total scores of the Treatment Outcome PTSD Scale and the patient-rated Davidson Trauma Scale and Sheehan Disability Scale (SDS). Depressive symptoms were assessed with the Montgomery-Asberg Depression Rating Scale. The proportion of patients achieving response and remission was also determined. RESULTS: 307 patients constituted the intent-to-treat population. At week 12, compared with the placebo group (N = 156), the paroxetine group (N = 151) showed significantly greater reduction of PTSD symptoms on both of the primary and all of the secondary outcome measures. Significantly greater improvement on the CAPS-2 total score was observed for paroxetine compared with placebo from week 4 (p < .05), and significantly greater proportions of paroxetine-treated patients achieved response (p < .001) and remission (p = .008) by week 12. The improvement in PTSD symptoms was similar in male and female patients. Functional improvement at the study endpoint was significantly greater (p < .05) in the paroxetine group in all 3 domains of the SDS (work, social life, family life). Treatment with paroxetine was well tolerated, with the frequency and type of adverse events recorded for the paroxetine group corresponding to the known safety profile of this medication. CONCLUSION: Paroxetine in doses of 20 to 50 mg once daily is effective as a treatment for chronic PTSD. Improvement is obtained for all 3 symptom clusters (reexperiencing, avoidance/numbing, hyperarousal) and is associated with significant reduction in disability after 12 weeks of treatment.

[A double-blind comparative study of the effectiveness and tolerance of paroxetine and amitriptyline in treatment of breast cancer patients with clinically assessed depression]. / Eine doppelblinde Vergleichsstudie zur Wirksamkeit und Verträglichkeit von Paroxetin und Amitriptylin bei der Behandlung von Brustkrebs-Patientinnen mit klinisch nachgewiesener Depression.

OBJECTIVE: In this double-blind, non-placebo controlled study [corrected], 179 patients with treated breast cancer who fulfilled the ICD-10 criteria for an acute depressive episode underwent an 8-week course of antidepressant treatment with either the tricyclic amitriptyline (75-150 mg, n = 87) or the serotonin-reuptake inhibitor paroxetine (20-40 mg, n = 88). METHODS: The change in clinical status relative to baseline was measured with the Montgomery-Asberg Depression Rating Scale (MADRS), the Clinical Global Impression (CGI), the Functional Living Index-Cancer (FLIC) and the Patient Global Evaluation. RESULTS: Both treatment groups showed significant improvement in all parameters at weeks 3, 5 and 8. At no time was there a significant difference in the efficacy of the antidepressants used. Adverse events, most of which were transitory, were reported by 53% of the patients in the paroxetine group and 60% in the amitriptyline group. The 8-week treatment was completed by 81% of the paroxetine and 76% of the amitriptyline patients. CONCLUSIONS: The results of this study show that depression in breast-cancer patients can be correctly diagnosed and adequately treated by non-psychiatrists. The treatment with both medications was carried out in dose ranges which correspond to that employed in physically well patients.

Paroxetine and amitriptyline augmentation of lithium in the treatment of major depression: a double-blind study.

To study the efficacy and safety of antidepressant augmentation of ongoing lithium therapy, lithium-maintained patients suffering from an breakthrough episode of major depression were randomly assigned under double-blind conditions to receive paroxetine 20 mg/day (N = 19) or amitriptyline 75 mg/day (N = 23). The initial dosages could be increased after 2 weeks to 40 mg/day and 150 mg/day, respectively, and the patients were treated for a total of 6 weeks. Efficacy was assessed weekly with the 21-item Hamilton Rating Scale for Depression (HAM-D) and the Clinical Global Impression Scale (CGI), and safety was assessed with the Dosage Record and Treatment Emergent Symptom Scale. After 4 weeks, a significantly greater proportion of patients in the paroxetine group had achieved a 50% reduction in baseline HAM-D scores, and the mean improvement in CGI severity of illness was significantly greater in the paroxetine group at weeks 3 and 5. The type and number of emergent events occurring during study treatment corresponded to the known side effect profiles of paroxetine and amitriptyline. Serum lithium levels were not affected by either antidepressant. The authors proposed that the more rapid improvement demonstrated by the group receiving the combination of lithium and paroxetine may be due to the synergistic serotonergic effects of these two medications.

The treatment of depression with paroxetine in psychiatric practice in Germany: the possibilities and current limitations of drug monitoring.

A drug monitoring of the antidepressant paroxetine was carried out in Germany from August 1992 to November 1993. The principal aim of this study was to collect demographic, diagnostic, efficacy, and medical-safety data regarding patients who were treated for up to 12 weeks with this SSRI. A secondary goal was the investigation of differences between patients who left treatment after 6 weeks or earlier and those who continued treatment. Evaluable data were obtained from 507 psychiatrists for 2817 patients, 1301 of whom extended treatment beyond 6 weeks. 64% of the patients had been pretreated for the current episode of depression. 50% were considered by their doctors to have either chronic or recurrent illness and 92% to possess moderate to severe symptomatology. Concomitant psychotropic medication was reported in 43% of cases, the most frequent medications being benzodiazepines, neuroleptics, and/or tricyclic antidepressants. Clear or complete improvement was noted for 63% of assessable patients by the end of week 6 and for 79% of the patients who extended treatment to 12 weeks. There were significantly more patients with DSM major depression and severe symptoms in the treatment-extender than in the 6-week treatment group. Paroxetine was tolerated well by most patients: of the 1009 adverse events reported, only 17 were considered "serious". There were no suicides or cases of overdose attributable to paroxetine. The discussion of these results is the basis for a critical appraisal of postmarketing-surveillance methodology. It is concluded that, despite its present structural weaknesses as compared to controlled investigations, drug monitoring of a new medication in the immediate postmarketing period can give insights into the treatment of large numbers of patients under private-practice conditions. However, drug monitoring as it is conducted in Germany can have different and perhaps conflicting functions which may limit its effectiveness. The authors recommend that all interested parties (physicians, the pharmaceutical industry, regulatory bodies) engage in a continuous dialog aimed at clearly formulating the goals and improving the methodology of drug monitoring.

The Tridimensional Personality Questionnaire in males at high and low risk for alcoholism.

Cloninger has proposed a tridimensional model as the basis for the classification of personality variants and has developed the Tridimensional Personality Questionnaire (TPQ) as an empirical test of this model. In this study, the TPQ was administered to two groups of young men. One group was comprised of nonalcoholic sons of male alcoholics; the other group consisted of nonalcoholic men with no family history of alcoholism. Since the sons of male alcoholics are considered to be at greater risk to develop alcoholism than the sons of nonalcoholics, it was hypothesized that the two groups would demonstrate differences with regard to one or more personality variants as measured by the TPQ. No statistically significant differences in the three TPQ-subscale scores of the two groups were found.