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Objective: Fluoxetine, paroxetine, sertraline, topiramate, and venlafaxine have previously shown efficacy for posttraumatic stress disorder (PTSD). One prior study using US Department of Veterans Affairs (VA) medical records data to compare these agents found no differences in symptom reduction in clinical practice. The current study addresses several weaknesses in that study, including limited standardization of treatment duration, inability to account for prior treatment receipt, use of an outdated symptomatic assessment for PTSD, and lack of functional outcome., Methods: A total of 834 VA outpatients were identified with DSM-5 clinical diagnoses of PTSD between October 2016 and March 2018 who initiated one of the medications and met prespecified criteria for treatment duration and dose, combined with baseline and endpoint DSM-5 PTSD Checklist (PCL-5) measurements. Twelve-week acute-phase changes in PCL-5 score and remission of PTSD symptoms were compared among patients receiving the different medications, as was use of acute psychiatric services in the subsequent 6-month continuation phase., Results: In the acute phase, patients improved by a mean of 6.8-10.1 points on the PCL-5 and 0.0%-10.9% achieved remission of PTSD symptoms. Those taking venlafaxine were significantly more likely to achieve remission (P = .008 vs fluoxetine and P < .0001 vs paroxetine, sertraline, and topiramate). In the continuation phase, there were no differences in acute psychiatric care use between medications. Those who continued their medication were less likely to use acute psychiatric services (HR = 0.55; P = .03)., Conclusions: There may be an advantage to venlafaxine over other agents in achieving acute-phase remission for DSM-5 PTSD in routine clinical practice, but this finding requires further study. Regardless of the agent chosen, medication cessation during the continuation phase is associated with a higher risk of acute psychiatric care use., (© Copyright 2020 Physicians Postgraduate Press, Inc.)

Objective: The objective of this study was to evaluate the efficacy of paroxetine in treating major depressive disorder (MDD) in persons with multiple sclerosis (MS)., Method: In this double-blind trial, 42 participants with MS and MDD were randomly assigned to one of two parallel 12-week treatment arms: paroxetine or placebo. The participants started at an initial dose of 10 mg/day paroxetine or placebo, titrated up to 40 mg daily based on symptoms response and side effects. The primary outcome measure was the Hamilton Rating Scale for Depression (HAM-D). Secondary outcomes included fatigue, anxiety and self-reported quality of life., Results: Intent-to-treat analyses revealed that both groups improved from pretreatment to posttreatment. Although the treatment group improved more than the control group on most measures, few differences were statistically significant. For the primary outcome, 57.1% of participants in the treatment arm had at least a 50% reduction in HAM-D score, compared with 40% in the control group (nonsignificant). Treatment effects were greater among the participants who completed the study; 78.6% of completers had a treatment response compared with 42.1% of controls (P=.073)., Conclusion: Although paroxetine may not be efficacious for all persons with MS and MDD, it appears to benefit some individuals.

(1) Between 20% and 30% of newborns exposed to selective serotonin reuptake inhibitor antidepressants (SSRIs) towards the end of gestation have disorders such as agitation, abnormal muscle tone and suction, seizures and hyponatraemia. (2) Worrisome data concerning a possible teratogenic effect were published in late 2005. (3) In a Danish cohort including 1054 pregnant women, the estimated relative risk of all congenital malformations, compared with the general population, among the offspring of women who received a prescription for an SSRI was 1.4 (95% CI 1.1-1.9), and the relative risk of cardiac malformations was 1.6 (95% CI 1.0-2.6). (4) An American retrospective study compared the newborns of women who were prescribed paroxetine during the first trimester of pregnancy with all newborns exposed to other antidepressants: 4% of newborns exposed to paroxetine had malformations (2% had cardiac malformations). The estimated relative risk for all congenital malformations was 2.20 (95% CI 1.34-3.63), and the estimated relative risk of cardiovascular malformations was 2.08 (95% CI 1.03-4.23). (5) Analysis of a Swedish birth register provided an estimated relative risk of cardiac malformations associated with paroxetine of 2.22 (95% CI 1.39-3.55) compared with the general population. (6) Another American study showed a global increase in the risk of malformations with paroxetine compared with all antidepressants. The risk of cardiovascular malformations was not significantly increased. (7) In a case-control study based on an American register of birth defects, the estimated relative risk of omphalocele was 3.0 with all SSRIs (95% CI 1.4 to 6.1), and the estimated relative risk of craniosynostosis was 1.8 (95% CI 1.0-3.2). (8) In practice, all SSRIs have been implicated in a possible increase in the risk of congenital malformations, but the most worrisome evidence concerns paroxetine. This potential risk implies that the justification for paroxetine treatment in pregnant women should be carefully weighed; this means double-checking the diagnosis, the potential benefits and adverse effects, and possible alternatives.

Background: Major depressive disorder is frequently a chronic, recurrent condition necessitating maintenance treatment. For some patients, compliance with daily pharmacotherapy is difficult over time. As an alternative approach, a once-weekly administered formulation of fluoxetine has recently been made available. This raises the important question of whether once-weekly enteric-coated fluoxetine, 90 mg, is effective for maintenance of response in patients whose depressive symptoms have responded to daily dosing with selective serotonin reuptake inhibitors (SSRIs) such as citalopram, paroxetine, or sertraline., Method: Patients had met DSM-IV criteria for major depressive disorder prior to beginning treatment for their current episode, had received 6 to 52 weeks of treatment with citalopram (20-40 mg/day [N = 83]), paroxetine (20 mg/day [N = 77]), or sertraline (50-100 mg/day [N = 86]), and had responded to that treatment (Clinical Global Impressions-Severity of Illness [CGI-S] score < or = 2, modified 17-item Hamilton Rating Scale for Depression [HAM-D-17] score < or = 10). Patients meeting these criteria (N = 246) continued treatment with their current SSRI for 1 week, then were switched to open-label enteric-coated fluoxetine, 90 mg, taken once weekly for 12 weeks. Safety measures were comparisons of spontaneously reported and solicited treatment-emergent adverse events. Efficacy measures were percentages of patients who discontinued the study for relapse and lack of efficacy and comparison of change from baseline to endpoint in scores on the modified HAM-D-17, subscales of the HAM-D-28, and the CGI-S. Quality of life measures were assessed with the MOS 36-Item Short-Form Health Survey (SF-36). We hypothesized that the once-weekly administration of fluoxetine could be safely and effectively initiated among subjects who had been stabilized on daily SSRI treatment., Results: Seventy-nine percent of patients successfully completed a switch to enteric-coated fluoxetine, 90 mg, with 9.3% discontinuing due to relapse or lack of efficacy. Enteric-coated fluoxetine at a once-weekly dose of 90 mg was well tolerated in all groups. No significant increases were found in the HAM-D-17 total, HAM-D-28 subscores, or CGI-S score. Patients showed improvement from baseline to endpoint in most of the SF-36 health concepts., Conclusion: Enteric-coated fluoxetine taken once weekly appears to be well tolerated and efficacious in patients who responded to acute therapy with other SSRIs and were subsequently switched to fluoxetine once weekly for continuation/maintenance therapy.