More robust evidence for the efficacy of lithium in the long-term treatment of bipolar disorder: should lithium (again) be recommended as the single preferred first-line treatment?

With two recent systematic reviews and meta-analyses on the efficacy of lithium compared to placebo and other treatment options, it can now be concluded that lithium is the only drug that has been shown efficacious in the prevention of any mood episodes, manic episodes and depressive episodes in randomised trials not enriched for prior response to and tolerance of lithium. It is argued that lithium should be recommended as the single preferred first-line drug in the long-term treatment of bipolar disorder

More robust evidence for the efficacy of lithium in the long-term treatment of bipolar disorder:should lithium (again) be recommended as the single preferred first-line treatment?

With two recent systematic reviews and meta-analyses on the efficacy of lithium compared to placebo and other treatment options, it can now be concluded that lithium is the only drug that has been shown efficacious in the prevention of any mood episodes, manic episodes and depressive episodes in randomised trials not enriched for prior response to and tolerance of lithium. It is argued that lithium should be recommended as the single preferred first-line drug in the long-term treatment of bipolar disorder

New vision on the mental problems of Vincent van Gogh; results from a bottom-up approach using (semi-)structured diagnostic interviews

Background: On July 29, 1890 at the age of 37 years, the Dutch painter Vincent van Gogh died from the consequences of a suicide attempt with a gun 2 days earlier. Since then many medical and psychological theories were suggested about what had happened to Van Gogh. Aim: To present an overview of the history of the mental problems of Van Gogh and the most likely diagnoses. Method: (Semi-)structured diagnostic interviews were applied to three art historians who are very familiar with Van Gogh from his correspondence and other sources as well as a neuropsychiatric examination to evaluate whether the symptoms might be explained by a medical condition. Results: Several previously suggested diagnoses could be excluded as being highly unlikely, while other diagnoses could be classified as more of less likely. Conclusion: Most likely Van Gogh suffered from comorbid illnesses. Since young adulthood, he likely developed a (probably bipolar) mood disorder in combination with (traits of) a borderline personality disorder as underlying vulnerability. This likely worsened through an alcohol use disorder combined with malnutrition, which then led, in combination with rising psychosocial tensions, to a crisis in which he cut off his ear. Thereafter, he likely developed two deliriums probably related to alcohol withdrawal, followed by a worsening with severe depressive episodes (of which at least one with psychotic features) from which he did not fully recover, finally leading to his suicide. As additional comorbidity, focal (temporal lobe) epilepsy cannot be excluded

A nationwide study on concordance with multimodal treatment guidelines in bipolar disorder

Background: Most previous studies on concordance with treatment guidelines for bipolar disorder focused on pharmacotherapy. Few studies have included other treatment modalities. Aims: To study concordance with the Dutch guideline of various treatment modalities in outpatient treatment settings for patients with bipolar disorder and to identity factors associated with concordance. Methods: A nationwide non-interventional study using psychiatrists’ and patients’ surveys. Results: 839 patients with bipolar or schizoaffective disorder bipolar type were included. Concordance with the guideline was highest for participation of a psychiatrist in the treatment (98%) and for maintenance pharmacotherapy (96%), but lower for supportive treatment (73.5%), use of an emergency plan (70.6%), psychotherapy (52.2%), group psychoeducation (47.2%), and mood monitoring (47%). Presence of a written treatment plan, a more specialized treatment setting, more years of education, and diagnosis of bipolar I disorder versus bipolar II, bipolar NOS, or schizoaffective disorder were significantly associated with better concordance. Conclusion: In contrast to pharmacotherapy, psychosocial treatments are only implemented to a limited extend in everyday clinical practice in bipolar disorder. More effort is needed to implement non-pharmacological guideline recommendations for bipolar disorder

Pharmacological treatment for psychotic depression

Background Evidence is limited regarding the most effective pharmacological treatment for psychotic depression: monotherapy with an antidepressant, monotherapy with an antipsychotic, another treatment (e.g. mifepristone), or combination of an antidepressant plus an antipsychotic. This is an update of a review first published in 2005 and last updated in 2015. Objectives 1. To compare the clinical efficacy of pharmacological treatments for patients with an acute psychotic depression: antidepressant monotherapy, antipsychotic monotherapy, mifepristone monotherapy, and the combination of an antidepressant plus an antipsychotic versus placebo and/or each other. 2. To assess whether differences in response to treatment in the current episode are related to non-response to prior treatment. Search methods A search of the Cochrane Central Register of Controlled Trials (CENTRAL), in the Cochrane Library; the Cochrane Common Mental Disorders Controlled Trials Register (CCMDCTR); Ovid MEDLINE (1950-); Embase (1974-); and PsycINFO (1960-) was conducted on 21 February 2020. Reference lists of all included studies and related reviews were screened and key study authors contacted. Selection criteria All randomised controlled trials (RCTs) that included participants with acute major depression with psychotic features, as well as RCTs consisting of participants with acute major depression with or without psychotic features, that reported separately on the subgroup of participants with psychotic features. Data collection and analysis Two review authors independently extracted data and assessed risk of bias in the included studies, according to criteria from the Cochrane Handbook for Systematic Reviews of Interventions. Data were entered into RevMan 5.1. We used intention-to-treat data. Primary outcomes were clinical response for efficacy and overall dropout rate for harm/tolerance. Secondary outcome were remission of depression, change from baseline severity score, quality of life, and dropout rate due to adverse effects. For dichotomous efficacy outcomes (i.e. response and overall dropout), risk ratios (RRs) with 95% confidence intervals (CIs) were calculated. Regarding the primary outcome of harm, only overall dropout rates were available for all studies. If the study did not report any of the response criteria as defined above, remission as defined here could be used as an alternative. For continuously distributed outcomes, it was not possible to extract data from the RCTs. Main results The search identified 3947 abstracts, but only 12 RCTs with a total of 929 participants could be included in the review. Because of clinical heterogeneity, few meta-analyses were possible. The main outcome was reduction in severity (response) of depression, not of psychosis. For depression response, we found no evidence of a difference between antidepressant and placebo (RR 8.40, 95% CI 0.50 to 142.27; participants = 27, studies = 1; very low-certainty evidence) or between antipsychotic and placebo (RR 1.13, 95% CI 0.74 to 1.73; participants = 201, studies = 2; very low-certainty evidence). Furthermore, we found no evidence of a difference in overall dropouts with antidepressant (RR 1.24, 95% CI 0.34 to 4.51; participants = 27, studies = 1; very low-certainty evidence) or antipsychotic monotherapy (RR 0.79, 95% CI 0.57 to 1.08; participants = 201, studies = 2; very low-certainty evidence). No evidence suggests a difference in depression response (RR 2.09, 95% CI 0.64 to 6.82; participants = 36, studies = 1; very low-certainty evidence) or overall dropouts (RR 1.79, 95% CI 0.18 to 18.02; participants = 36, studies = 1; very low-certainty evidence) between antidepressant and antipsychotic. For depression response, low- to very low-certainty evidence suggests that the combination of an antidepressant plus an antipsychotic may be more effective than antipsychotic monotherapy (RR 1.83, 95% CI 1.40 to 2.38; participants = 447, studies = 4), more effective than antidepressant monotherapy (RR 1.42, 95% CI 1.11 to 1.80; participants = 245, studies = 5), and more effective than placebo (RR 1.86, 95% CI 1.23 to 2.82; participants = 148, studies = 2). Very low-certainty evidence suggests no difference in overall dropouts between the combination of an antidepressant plus an antipsychotic versus antipsychotic monotherapy (RR 0.79, 95% CI 0.63 to 1.01; participants = 447, studies = 4), antidepressant monotherapy (RR 0.91, 95% CI 0.55 to 1.50; participants = 245, studies = 5), or placebo alone (RR 0.75, 95% CI 0.48 to 1.18; participants = 148, studies = 2). No study measured change in depression severity from baseline, quality of life, or dropouts due to adverse events. We found no RCTs with mifepristone that fulfilled our inclusion criteria. Risk of bias is considerable: we noted differences between studies with regards to diagnosis, uncertainties around randomisation and allocation concealment, treatment interventions (pharmacological differences between various antidepressants and antipsychotics), and outcome criteria. Authors' conclusions Psychotic depression is heavily under-studied, limiting confidence in the conclusions drawn. Some evidence indicates that combination therapy with an antidepressant plus an antipsychotic is more effective than either treatment alone or placebo. Evidence is limited for treatment with an antidepressant alone or with an antipsychotic alone. Evidence for efficacy of mifepristone is lacking