Georgios D. Kotzalidis

The International Society for Bipolar Disorders (ISBD) Task Force Report on Antidepressant Use in Bipolar Disorders

OBJECTIVE The risk-benefit profile of antidepressant medications in bipolar disorder is controversial. When conclusive evidence is lacking, expert consensus can guide treatment decisions. The International Society for Bipolar Disorders (ISBD) convened a task force to seek consensus recommendations on the use of antidepressants in bipolar disorders. METHOD An expert task force iteratively developed consensus through serial consensus-based revisions using the Delphi method. Initial survey items were based on systematic review of the literature. Subsequent surveys included new or reworded items and items that needed to be rerated. This process resulted in the final ISBD Task Force clinical recommendations on antidepressant use in bipolar disorder. RESULTS There is striking incongruity between the wide use of and the weak evidence base for the efficacy and safety of antidepressant drugs in bipolar disorder. Few well-designed, long-term trials of prophylactic benefits have been conducted, and there is insufficient evidence for treatment benefits with antidepressants combined with mood stabilizers. A major concern is the risk for mood switch to hypomania, mania, and mixed states. Integrating the evidence and the experience of the task force members, a consensus was reached on 12 statements on the use of antidepressants in bipolar disorder. CONCLUSIONS Because of limited data, the task force could not make broad statements endorsing antidepressant use but acknowledged that individual bipolar patients may benefit from antidepressants. Regarding safety, serotonin reuptake inhibitors and bupropion may have lower rates of manic switch than tricyclic and tetracyclic antidepressants and norepinephrine-serotonin reuptake inhibitors. The frequency and severity of antidepressant-associated mood elevations appear to be greater in bipolar I than bipolar II disorder. Hence, in bipolar I patients antidepressants should be prescribed only as an adjunct to mood-stabilizing medications.

Factors associated with initial treatment response with antidepressants in bipolar disorder.

INTRODUCTION Controversy in antidepressant (AD) use in bipolar depression relies in its potential induction of mood switches and ineffectiveness. Responders to acute AD add-on treatment maintain response with continued treatment, whilst partial/non-responders fail to reach remission despite continuation treatment. We aimed to identify response predictors to acute AD addition in bipolar depression in order to optimize treatment choice in bipolar depression and avoid unnecessary AD exposure of people unlikely to respond. METHODS Two hundred and twenty-one DSM-IV-TR depressed bipolar - type I and II - patients were treated with AD on an observational study. AD response was defined as an at least 50% drop from baseline of their HDRS17 score after 8weeks of treatment. One hundred and thirty-eight patients (138, 62.4%) fulfilled response criteria (RI) whilst 83 patients (37.6%) did not (NRI). In all cases AD therapy was on top of previously prescribed stabilizers and/or atypical antipsychotics. RESULTS RI patients were more likely to have had previous response to ADs, whereas NRI had a higher number of previous mood switches with ADs during past depressive episodes. Psychotic symptoms were more frequent amongst RI, whilst lifetime history of atypical depression was more frequent amongst NRI. NRI had more total, depressive, and hypomanic, but not manic or mixed, episodes in the past than RI. Analyzed through a logistic regression, higher previous response to ADs and lower rate of past hypomanic episodes in RI were the variables explaining intergroups (RI vs. NRI) differences. DISCUSSION Taking into account the proper caution in the use of Ads in bipolar disorder, there is a subgroup of bipolar patients who might benefit from adjunctive Ads. Looking at specific clinical factors during the course of the illness could help physicians in deciding whether to use an antidepressant in a bipolar depressed patient already treated with mood stabilizers.

Effectiveness of Short-Term Olanzapine in Patients With Bipolar-I Disorder, With or Without Comorbidity With Substance Use Disorder

Objectives Prognosis of comorbid bipolar disorder (BD) and drug abuse is poor. We assessed the efficacy of olanzapine in manic or mixed BD patients, with (SUD) or without (N-SUD) comorbidity with substance use disorder (SUD) and its effect on drug abuse, days of abuse, and craving. Methods Eighty patients with BD-I (40 SUD) were hospitalized for a manic or mixed episode and received add-on olanzapine. Assessments were conducted at admission, discharge, and 4 and 8 weeks after discharge. Primary outcome was the proportion of responders and remitters in each group. We used a logistic regression model to adjust for possible confounders. We assessed craving and drug-abuse days with a visual analog scale and the Timeline Follow-Back. Results SUD and N-SUD were similar on response and remission, adjusted for sex, age, years ill, age at first episode, first episode depressive, number of hospitalizations, and duration of hospitalization (odds ratio, 1.09; 95% confidence interval, 1.02–2.29). Mood rating scores dropped significantly from baseline to end point in both groups. Timeline follow-back decreased in SUD from 22.5 to 7.3 at 8 weeks postdischarge, whereas craving dropped from 8.3 to 5.1 (P < 0.03). Conclusions The effectiveness of short-term olanzapine in BD-I mania or mixed mania did not differ according to SUD comorbidity. Treatment was followed by less substance use/abuse and craving in comorbid bipolar-SUD patients.

Clinical stabilisation with lacosamide of mood disorder comorbid with PTSD and fronto-temporal epilepsy

Background and aim of the work: Mood disorders are often complicated by comorbidity with epilepsy. Anxiety and personality disorders may worsen prognosis and treatment outcome. Lacosamide has been recently introduced as adjunctive treatment for partial epilepsy. Its mechanism consists of selective slow inactivation of voltage-gated sodium channels, thus promoting an extended stabilisation of cell membranes. Antiepileptic drugs have been largely used since the 1950s in psychiatry as mood stabilisers due to their membrane stabilising and anti-kindling effects. Like lithium, antiepileptic drugs are first choice treatment for Bipolar and Cyclothymic Disorders. Methods: We tested the efficacy of the most recent antiepileptic medication, lacosamide, in a patient with simultaneously occurring cyclothymic disorder, severe post-traumatic stress disorder, and fronto-temporal epilepsy. Lacosamide was titrated up to 200 mg/day, added to ongoing 750 mg/day lithium, 15 mg/day oral aripiprazole then switched to 400 mg/month long-acting aripiprazole, and 2 mg/day A-desmethyldiazepam. Results: We observed EEG normalisation one month later, along with reduced anxiety and an additive effect to lithium-induced stabilisation of mood fluctuations since the second week of lacosamide addition. Conclusions: Further studies with this drug in the bipolar spectrum are warranted. (www.actabiomedica.it)