Effects of Treatment Discontinuation in Clinical Psychopharmacology

Baldessarini, Ross J.; Tondo, Leonardo

doi:10.1159/000497334

Cited by 41 publications

(62 citation statements)

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“…Sexual dysfunction is reported to occur in 40–60% of patients with major depressive disorder (MDD), is common in both men and women (Montejo et al, 2019; Montejo, Montejo, & Baldwin, 2018; Perlis et al, 2009; Seidman, 2006), and sexual dysfunction is reported to increase the risk of the development of MDD by 130–210% (Atlantis & Sullivan, 2012; Kennedy & Rizvi, 2009; Saragoussi et al, 2017). In patients with MDD, sexual dysfunction leads to poorer outcomes, and negatively affects medication adherence (Ashton, Jamerson, Weinstein, & Wagoner, 2005; Francois, Levin, Kutscher, & Asemota, 2017; Sansone & Sansone, 2012), which impacts the response to treatment for MDD (Baldessarini & Tondo, 2019), and is associated with impaired quality of life and increased rates of depression relapse (Ishak et al, 2013; Nurnberg, 2008; Saragoussi et al, 2017; Touya, Diamand, Saragoussi, & Francois, 2017; Williams, Edin, Hogue, Fehnel, & Baldwin, 2010).…”

Section: Introductionmentioning

confidence: 99%

Improvement of sexual functioning during treatment of MDD with adjunctive pimavanserin: A secondary analysis

et al. 2020

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Background: Sexual dysfunction is common among patients with major depressive disorder (MDD). In the CLARITY study, the safety and efficacy of adjunctive pimavanserin, an inverse agonist at 5-HT 2A receptors, were demonstrated when added to existing treatment for MDD. This analysis provides a detailed assessment of the effects of pimavanserin on sexual function from the CLARITY study. Methods: Patients with a diagnosis of MDD in a depressive episode, inadequate response to ongoing antidepressant therapy, and a Montgomery-Åsberg Depression Rating Scale total score >20 were randomized to pimavanserin 34 mg/day or placebo added to ongoing treatment with an immediate revision of all selective serotonin or serotonin-norepinephrine for 5 weeks (Stage 1), and nonresponders (<50% improvement from baseline in Hamilton Depression Rating Scale [HAMD-17]) were re-randomized for an additional 5 week (Stage 2). Effects of pimavanserin on the Massachusetts General Hospital Sexual Functioning Index (MGH-SFI) and HAMD-17 Item 14 (sexual interest) were examined. Results: Among 203 patients (51 on pimavanserin; 152 on placebo), pimavanserin demonstrated significant improvement from baseline to Week 5 on the MGH-SFI (least square [LS]mean difference −0.634, 95% confidence interval [CI] [−0.964, −0.304]; p = .0002; effect size [ES], Cohen's d: .614). Across Stages 1 and 2, the weighted LSmean difference was −0.468 (95% CI [−0.720, −0.216]; p = .0003) for pimavanserin versus placebo. Mean changes from baseline to Week 5 for MGH-SFI Items 1, 2, 3, and 5 and HAMD Item 14 were significantly (p < .05) greater with pimavanserin versus placebo. Conclusions: Adjunctive pimavanserin improved sexual function in patients with MDD. Adding pimavanserin to ongoing treatment for MDD may be especially useful for patients experiencing sexual dysfunction. K E Y W O R D S adjunctive, major depressive disorder, pimavanserin, sexual function

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Section: Introductionmentioning

confidence: 99%

Improvement of sexual functioning during treatment of MDD with adjunctive pimavanserin: A secondary analysis

et al. 2020

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“…4,5 Adverse clinical effects of discontinuing psychotropic drugs also can arise in changing from active drug to placebo in clinical trials. 6,7 Pharmacodynamic mechanisms underlying discontinuation syndromes…”

Section: Withdrawal Reactionsmentioning

confidence: 99%

“…It is likely that complex pharmacodynamic adaptations to long-term drug treatment are involved. 6,8,9 Long-term exposure to antidepressant, antipsychotic, anxiolytic, mood stabilising and other psychotropic drugs leads to neuropharmacological adaptations that include changes in postsynaptic receptor and autoreceptor sensitivity, neurotransmitter synthesis and release, and various downstream molecular and genetic mechanisms in multiple brain systems. 8,9 Agents with long elimination half-lives appear to carry lower risk of withdrawal effects, including fluoxetine among antidepressants and long-acting antipsychotics.…”

Section: Withdrawal Reactionsmentioning

confidence: 99%

“…Restoring the withdrawn medicine, even temporarily and at lower doses, sometimes may reduce the clinical manifestations of withdrawal reactions. 6 Later adverse clinical effects of drug discontinuation…”

Section: Withdrawal Reactionsmentioning

confidence: 99%

“…We have reported on adverse clinical effects of discontinuing longterm treatment with antidepressants and antipsychotics as well as lithium. 6,9,[12][13][14]18 Such effects may also occur in patients with bipolar disorder following discontinuation of maintenance treatments other than with lithum. 17 Of particular interest, abrupt or rapid (1-14 days) versus slower discontinuation of lithium was consistently associated with earlier recurrences of illness and increased risk or suicide attempts or fatalities in patients with bipolar disorder.…”

Section: Effects Of Discontinuation Ratementioning

confidence: 99%

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Discontinuing psychotropic drug treatment

Tondo

Baldessarini

2020

BJPsych open

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Summary Interruption of ongoing treatment with benzodiazepines, antidepressants, antipsychotics and mood stabilisers including lithium can be followed by clinically significant withdrawal reactions within hours or days, as well as later increases in relapses or recurrences of the illness being treated. Such observations support the view that stopping treatment is not equivalent to being untreated. With lithium, antipsychotics and antidepressants, there is consistent evidence that abrupt or rapid discontinuation is followed by earlier clinical worsening than with more gradual removal of treatment. Moreover, treatment discontinuation can complicate interpretation of responses to changes in treatment, including in clinical practice and in experimental treatment trials. Notably, terminating preceding treatments can lead to both discontinuation and carry-over effects that can have an impact on the interpretation of observed outcomes.

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Sequential Combination of Pharmacotherapy and Psychotherapy in Major Depressive Disorder

Guidi

Fava

2021

JAMA Psychiatry

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IMPORTANCEThe sequential model emerged from the awareness that the persistence of residual symptoms and the frequent occurrence of psychiatric comorbidity were both associated with poor long-term outcome of major depressive disorder (MDD).OBJECTIVE To conduct an updated meta-analysis to examine the association of the sequential combination of pharmacotherapy and psychotherapy with reduced risk of relapse and recurrence in MDD.DATA SOURCES Keyword searches were conducted in PubMed, PsycInfo, Web of Science, and the Cochrane Library from inception of each database through November 2019. Reference lists from relevant studies were examined using the following keywords: sequential treatment, drugs and psychotherapy, combined treatment, continuation or maintenance, relapse or recurrence and prevention, and depress* or major depress*, selecting adults and randomized controlled trials as additional limits. Authors of selected articles were contacted if needed.STUDY SELECTION Randomized clinical trials examining the effectiveness of the sequential use of psychotherapy following response to acute-phase pharmacotherapy in the treatment of adult remitted patients with MDD were selected independently by 2 reviewers. DATA EXTRACTION AND SYNTHESISThe methods used fulfilled the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) reporting guideline. Data extraction and methodologic quality assessment were conducted independently by the reviewers. Examination of the pooled results was performed based on the random-effects model. Heterogeneity between study results and likelihood of significant publication bias were assessed. Sensitivity analyses and meta-regressions were also run. MAIN OUTCOMES AND MEASURESThe primary outcome measures were relapse or recurrence rates of MDD, as defined by study investigators, at the longest available follow-up. RESULTSSeventeen randomized clinical trials met criteria for inclusion in the meta-analysis, with 1 study yielding 2 comparisons (2283 patients overall, with 1208 patients in a sequential treatment arm and 1075 in a control arm). The pooled risk ratio for relapse/recurrence of MDD was 0.84 (95% CI, 0.74-0.94), suggesting a relative advantage in preventing relapse/recurrence for the sequential combination of treatments compared with control conditions. CONCLUSIONS AND RELEVANCEThe results of this systematic review and meta-analysis indicate that the sequential integration of psychotherapy following response to acute-phase pharmacotherapy, alone or combined with antidepressant medication, was associated with reduced risk of relapse and recurrence in MDD. The preventive value of the sequential strategy relies on abatement of residual symptoms and/or increase in psychological well-being. The steps for implementing the sequential approach in remitted patients with recurrent MDD are provided.

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Effects of Treatment Discontinuation in Clinical Psychopharmacology

Cited by 41 publications

References 41 publications

Improvement of sexual functioning during treatment of MDD with adjunctive pimavanserin: A secondary analysis

Improvement of sexual functioning during treatment of MDD with adjunctive pimavanserin: A secondary analysis

Discontinuing psychotropic drug treatment

Sequential Combination of Pharmacotherapy and Psychotherapy in Major Depressive Disorder

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