Treating bipolar depression – antidepressants and alternatives: a critical review of the literature

Filippis

Crescenzo

2019

Acta Psychiatr Scand

Pramipexole in the treatment of unipolar and bipolar depression. A systematic review and meta-analysis Tundo A, de Filippis R, De Crescenzo F. Pramipexole in the treatment of unipolar and bipolar depression. A systematic review and metaanalysis Objective: Several depressed patients do not respond to traditional antidepressants. Our aim was to systematically review the effectiveness and safety of pramipexole in unipolar and bipolar depression. Methods: We conducted a systematic review of randomized clinical trials (RCTs) and observational studies on pramipexole for patients with major depressive episodes, following PRISMA guidelines. Our primary outcome measure was treatment response at endpoint. The study protocol was registered on PROSPERO: CRD42018108699. Results: We found five RCTs, three open-label trials and five observational studies, with 504 participants (57% women; mean age, 45.3 years; mean sample size, 39; median duration of treatment, 8 weeks; mean follow-up duration, 45 weeks; mean maximum dose, 1.62 mg). We found an overall short-term response rate of 52.2% and remission rate of 36.1%, and an overall long-term response rate of 62.1% and remission rate of 39.6%. In RCTs, patients treated with pramipexole had a superior response rate compared with placebo (RR: 1.77; 95% CI: 1.11-2.82) and similar to SSRIs (RR: 0.93; 95% CI: 0.44-1.95). Acceptability and tolerability were good, with nausea being the most frequent side-effect. Conclusion: Our study found some evidence for an effect of pramipexole for the treatment of major depressive episodes. Summations• Results from clinical trials found that pramipexole for major depressive episodes is superior to placebo and similar to SSRIs.• The use of pramipexole as antidepressant appears to be safe, with nausea being the most frequent side-effect.• Some side-effects commonly reported in studies on individuals with Parkinson's diseasesuch as lethargy, gambling, hypersexuality and compulsive shoppingare not reported for individuals treated with pramipexole for major depressive episodes. Limitations• Our systematic review includes only few studies.• The small sample size of the studies suggests that we are in an early phase of research and that a phase 3 trial is needed before drawing clinical conclusions.

Section: Discussionsupporting

confidence: 91%

Pramipexole in the treatment of unipolar and bipolar depression. A systematic review and meta‐analysis

Filippis

Crescenzo

2019

Acta Psychiatr Scand

“…In the past Tundo, Cavalieri, Navari, and Marchetti (2011) hypothesized that AD acute treatment is effective and safe for some bipolar depressed patients and ineffective and/or unsafe for others, underscoring the need to identify more homogeneous phenotypes of bipolar depression based on treatment outcome. This hypothesis has been supported by the results of a single site observational study, showing that in a sample of bipolar depressed patients-selected according to the partially modified recommendations of the International Society for Bipolar Disorder's (ISBD) task force on AD use in bipolar disorders (Pacchiarotti et al, 2013) -adjunctive AD to MDs and/or SGA is effective in bipolar depression as well as in unipolar depression and does not increase the risk of switch or of suicide attempts (Tundo, Calabrese, Proietti, & de Filippis, 2015a).…”

mentioning

confidence: 99%

Is short‐term antidepressant treatment effective and safe in bipolar depression? Results from an observational multicenter study

Human Psychopharmacology

Musetti

Grande

et al. 2020

Self Cite

Objectives: To investigate the short-term effectiveness and the short-term and long-term safety of acute antidepressant (AD) treatment of bipolar depression in a naturalistic setting.Methods: Patients with bipolar (n = 86) or unipolar (n = 111) depression were consecutively recruited and treated with AD (combined with mood stabilizer [MS] and/or second-generation antipsychotics in bipolar depression). Exclusion criteria were mixed depression, high mood instability, previous predominantly mixed depression (both bipolar and unipolar depression), rapid cycling course and previous switch AD-emerging (bipolar depression).Results: After 12 weeks of treatment, no difference was found in remission, response and improvement rates between bipolar and unipolar depression. Concerning short-term safety, switching and suicidality did not differ significantly between the two groups, and no suicide attempt was observed. Concerning long-term safety, patients with bipolar depression had a significant reduction of depressive and total recurrences during the year of follow-up, compared to the year before entering the study, without significant changes in (hypo)mania and mixed depression recurrences, and suicide rates.Conclusions: Acute AD treatment of bipolar depression is effective in the shortterm and safe in the short-and long-term, when administered in combination with MSs and/or second-generation antipsychotics, with a low risk of switch, mixed depression and cycle acceleration.

“…The long-term use of antidepressants in patients with BD is a particularly controversial topic and has been associated with an increased risk of (hypo)manic or mixed state switch and cycle acceleration in some but not in other studies (Amit & Weizman, 2012;Pacchiarotti et al, 2013; Tundo, Cavalieri, Navari, & Marchetti, 2011;Vázquez, Tondo, Undurraga, & Baldessarini, 2013).…”

Section: Discussionmentioning

confidence: 99%

Lithium, valproate, and carbamazepine prescribing patterns for long‐term treatment of bipolar I and II disorders: A prospective study

Musetti

Human Psychopharmacology

Benedetti

et al. 2018

Self Cite

Objective This study aims to describe the prescription patterns of the mood stabilizers most commonly used for the treatment of bipolar I and II disorders (lithium, valproate, and carbamazepine) and to analyze the treatment outcomes. Methods Two hundred and thirty‐four outpatients with bipolar disorders receiving prophylactic treatment with lithium, valproate, carbamazepine, or their combination were followed up for at least 18 months in two Italian psychiatric centers specialized in mood disorders. Results The combination of lithium and valproate or carbamazepine was the most common prophylactic treatment (54.3%), followed by valproate or carbamazepine (24%) and lithium monotherapy (22%). Polytherapy was prescribed mainly to patients with bipolar I disorder, a high number of previous episodes and lifetime psychotic symptoms, whereas valproate or carbamazepine monotherapy was prescribed to patients with anxiety comorbidity. The annual frequency of recurrences decreased significantly after entering the study in the overall sample, and the reduction was significantly higher in patients on lithium plus valproate or carbamazepine compared with the valproate or carbamazepine group, but not with the lithium monotherapy group. The number of mixed recurrences during the follow‐up was significantly higher in patients on lithium plus valproate or carbamazepine. Conclusions Our findings may help clinicians to personalize long‐term treatment to prevent relapses of bipolar disorder according to clinical presentation.