A “community-friendly” version of integrated group therapy for patients with bipolar disorder and substance dependence: A randomized controlled trial

Background

Integrated group therapy, a new treatment for patients with bipolar disorder and substance use disorder, has previously been found to be efficacious in reducing substance use, but its length (20 sessions) and need for highly trained therapists may limit its adoption in substance use disorder community treatment programs. This paper compares a briefer (12 session) version of integrated group therapy, led by substance use disorder counselors without previous cognitive-behavioral training or bipolar disorder experience, to group drug counseling.

Methods

Sixty-one patients with bipolar disorder and substance dependence, taking mood stabilizers, were randomized to 12 sessions of integrated group therapy (n = 31) or group drug counseling (n = 30).

Results

Analyses of primary outcomes showed trends favoring integrated group therapy, with greater reduction in substance use during follow-up and a greater decline in risk of mood episodes during treatment. Secondary analyses favored integrated group therapy, with a significantly greater likelihood of achieving total abstinence, a significantly shorter time to the first abstinent month, and a significantly greater likelihood of achieving a “good clinical outcome” (a composite measure encompassing both substance use and mood simultaneously).

Conclusions

A shortened version of integrated group therapy can be delivered successfully by substance use disorder counselors, with better overall outcomes than those achieved with group drug counseling.     

Relation between cigarette smoking and cognitive function in euthymic individuals with bipolar disorder

Background

Individuals with bipolar disorder have higher rates of cigarette smoking and cognitive deficits when compared to the general population. Emerging evidence indicates that both smoking and cognitive deficits are associated with more severe illness presentation and course.

Methods

The data were derived from a study evaluating a novel treatment for cognitive function in bipolar disorder. Smoking status was determined by self-report; cognitive function was evaluated with a comprehensive cognitive battery, which included measures of psychomotor speed, attention, memory, learning and executive function. The relations between smoking status and cognitive measures were evaluated with two independent-samples t-test and multiple regression.

Results

The sample comprised forty-three subjects with bipolar disorder (Type I/II). There were no consistent differences in neuropsychological performance between current smokers (N = 16) and non-smokers (N = 27) on most tasks. The occurrence of subjective cognitive failures, as measured with the Cognitive Functioning Questionnaire, was non-significantly lower for smokers compared to non-smokers. Lifetime “smoking load” was negatively associated with premorbid intelligence as estimated by the National Adult Reading Test.

Conclusion

This pilot study provides preliminary evidence that cigarette smoking may exert a salutary effect on subjective, but not objective, measures of cognitive function in euthymic bipolar patients. A larger sample size evaluating this hypothesis would be less vulnerable to type II error.     

Patterns of response to antidepressants in major depressive disorder: Drug resistance or worsening of depression are associated with a bipolar diathesis

Resistance and worsening of depression in response to antidepressants (ADs) are major clinical challenges. In a large international sample of patients with major depressive disorder (MDD), we aim to explore the possible associations between different patterns of response to ADs and bipolarity. A total of 2811 individuals with a major depressive episode (MDE) were enrolled in the BRIDGE-II-MIX study. This post-hoc analysis included only 1329 (47%) patients suffering from MDD. Patients with (TRD-MDD, n = 404) and without (NTRD-MDD, n = 925) history of resistance to AD treatment and with (n = 184) and without (n = 1145) previous AD-induced irritability and mood lability (AIM) were compared using Chi-square, t-Student's test and logistic regression models. TRD-MDD patients resulted significantly associated with higher rates of AIM, psychotic features, history of suicide attempts, emotional lability and impulsivity, comorbid borderline personality disorder and polipharmacological treatment, compared to NTRD-MDD group. In comparison to NAIM-MDD patients, subjects in the AIM-MDD group showed significantly higher rates of first-degree family history for BD, previous TRD, atypical features, mixed features, psychiatric comorbidities, lifetime suicide attempts and lower age at first psychiatric symptoms. In addition, patients with AIM presented more often almost all the hypomanic symptoms evaluated in this study. Among these latter symptoms, logistic regressions showed that distractibility, impulsivity and hypersexuality were significantly associated with AIM-MDD. In conclusion, in MDD patients, a lifetime history of resistance and/or irritability/mood lability in response to ADs was associated with the presence of mixed features and a possible underlying bipolar diathesis.     

Zonisamide for bipolar disorder, mania or mixed states: a randomized, double blind, placebo-controlled adjunctive trial

Objective

This is the first multicenter, double blind, randomized, placebo-controlled trial to evaluate the safety and efficacy of adjunctive zonisamide for the treatment of bipolar mania or mixed state.

Experimental design

One hundred four patients with Bipolar Disorder, Type I, II or NOS, in a manic, hypomanic or mixed state of illness were randomized to either adjunctive zonisamide or placebo. The study consisted of three phases: a 7 to 30 day screening and stabilization phase, 6 weeks of blinded treatment and a 1 to 3 week discontinuation phase. The primary outcome variable for manic and hypomanic patients was the Young Mania Rating Scale (YMRS) both the YMRS and Montgomery Asberg Depression Rating Scale (MADRS) served as primary outcome variables for patients in mixed states. Secondary outcome measures included the Clinical Global Impression for Bipolar Disorder (CGI-BP), the Quality of Life Enjoyment and Satisfaction Questionnaire (Q-LES-Q) and an a priori analysis of response and remission. Metabolic parameters including weight, waist-hip ratio, body mass index, fasting glucose, cholesterol and triglyceride levels were also analyzed. Side effects were measured using the SAFTEE.

Principal observations

There were no statistically significant differences for any of the primary or secondary outcome measures between zonisamide and placebo-treated patients.

Conclusions

In contrast to previous studies that suggested efficacy of adjunctive zonisamide in bipolar mania or mixed state, these results were not confirmed in this double blind controlled study.     

Changes in the prescribing pattern of antidepressant drugs in elderly patients: an Italian,nationwide, population-based study

Background

Despite the high use of antidepressants (ADs) among the elderly, there is limited information about the prescribing pattern of these drugs in the Italian elderly population. The aim of this study was to analyze the trend in the use of ADs in the Italian elderly patients in the years 2003-2009, and specifically, to evaluate rates and predictors of AD treatment discontinuation in depressed older patients.

Methods

The nationwide general practice Health Search Database (HSD) was used to identify AD users aged 65 years old and over from 2003 to 2009. ADs were categorized as (1) selective serotonin reuptake inhibitors (SSRIs); (2) serotonin-norepinephrine reuptake inhibitors (SNRIs); (3) tricyclic antidepressants (TCAs); (4) noradrenergic and specific serotonergic antidepressants (NaSSAs); and (5) other ADs. Incidence and prevalence of AD use per 1,000 inhabitants was calculated by drug class and single compound. We also measured rates and predictors of AD discontinuation (i.e., treatment gap?≥?60 days) during the first year of therapy.

Results

Overall, 39,557 AD users ≥65 years (17 % of the total HSD elderly population) were included in the study. SSRIs were increasingly and most frequently prescribed ADs (102.7-195.3 per 1,000 over seven years). The most common indications for AD use were depression and anxiety. Overall, 14 % of AD users continued their AD medication without treatment gaps, 27 % were intermittent AD users and 58 % discontinued their ADs during the first year of follow-up. Specific AD classes such as TCAs and ‘other ADs were found to be predictors of discontinuation. In depressed patients, the use of NaSSas, TCAs and ‘other ADs as well the concomitant use of >5 drugs (other than ADs) and living in Southern Italy were more likely to predict discontinuation.

Conclusion

ADs, especially SSRIs, are widely and increasingly prescribed in elderly Italian patients in recent years. The observed high AD discontinuation rates are likely to impact the achievement of a therapeutic endpoint in depressed patients. Patients who are at high risk of AD discontinuation such as those receiving multi-drug therapy or living in Southern Italy should be monitored more closely to improve benefits of AD treatments.     

Zonisamide for Bipolar Depression: A Randomized,Double Blind,Placebo-Controlled,Adjunctive Trial

Objective

This is the first multicenter, double blind, randomized, placebo-controlled trial to evaluate the safety and efficacy of adjunctive zonisamide for the treatment of bipolar depression.

Experimental design

One hundred two patients with bipolar disorder, type I or II in the depressed phase of illness were randomized to either adjunctive zonisamide or placebo. The study consisted of three phases, a 7 to 30 day screening and stabilization phase, 6 weeks of blinded treatment and a 1 to 3 week discontinuation phase. MADRS score was the primary outcome variable. Secondary outcome measures included the YMRS, CGI-S, CGI-I, Quality of Life Enjoyment and Satisfaction Questionnaire (Q-LES-Q), and an a priori analysis of response and remission. Metabolic parameters including weight, waist-hip ratio, body mass index, fasting glucose, cholesterol and triglyceride levels were also evaluated. Side effects were measured using the SAFTEE.

Principal observations

There were no statistically significant differences in response between subjects treated with adjunctive zonisamide vs. placebo controls for the primary or secondary outcome measures. There were also no differences between the groups with regard to response rate or remission rate.

Conclusions

In contrast to preliminary open label studies that suggested a role for zonisamide in bipolar depression, we could not confirm these results in a large double blind controlled study.     

Burden of bipolar depression: impact of disorder and medications on quality of life

Bipolar disorder is a complex, chronic psychiatric condition characterized by recurring episodes of depressive illness and mania or hypomania. Although the manic or hypomanic episodes define the disorder, recent research has shown that depressive symptoms predominate over manic symptoms in the majority of patients, and that bipolar depression accounts for much of the significant morbidity and mortality associated with bipolar disorder. Given these findings, there has been a recent upsurge of interest in furthering our understanding of the burden of depression in bipolar disorder. At the same time, increasing scientific attention is now being paid to expanding the measurement of outcome in bipolar disorder to encompass broader indicators of response, one of which is the assessment of quality of life (QOL). In this review, we provide a summary of the current knowledge about QOL in the depressive phase of bipolar disorder, and the effects of pharmacological treatment interventions for bipolar disorder upon QOL. It appears that QOL is poorer in bipolar disorder than in other mood disorders and anxiety disorders, but that schizophrenia might compromise QOL more severely than bipolar disorder. Existing data also suggest that, for patients with bipolar disorder, QOL is negatively associated with depression, both as a cross-sectional mood state and perhaps also as a feature of the patient's course. Despite its clinical and public health importance, bipolar depression has only recently started to receive the attention it warrants in clinical trials, and many important questions about its optimal pharmacological management remain to be answered. There is also a paucity of information about the impact of pharmacological interventions on QOL in bipolar depression. To our knowledge, only two clinical trials to date have specifically examined the impact of medications on QOL in patients with bipolar depression. A small number of other studies have examined the effects of depressive symptoms on QOL in patients who are experiencing manic or mixed episodes. Nonetheless, QOL appears to be a meaningful and important indicator of outcome and recovery in this patient population, and one that warrants further scientific interest and energy.     

Substance use disorders increase the odds of subsequent mood disorders

Background

There is a well-known association between mood disorders and substance use disorders (SUD), but little research has been conducted on SUDs as risk factors for the development of subsequent mood disorders.

Methods

We analyzed data from the National Comorbidity Survey Replication study. Diagnoses were determined using DSM-IV criteria. Odds ratios (aORs) of subsequently developing mood disorders were adjusted for age, sex and race/ethnicity.

Results

Data from 5217 individuals were included (6.6% male; mean age 45.3 years; 72.6% White, 11.2% Black, 12.5% Hispanic and 3.7% other). Subsequent mood disorders developed in 26.4% of individuals with primary adolescent-onset SUD (12–17 years), 21.7% of those with SUD onset at 18–25 years, and 14.0% of those with SUD onset between the ages of 26 and 34 years. The mean lagtime between SUD onset and development of a mood disorder was about 11 years. Controlling for demographic variables, the aORs of developing a mood disorder in these three age groups were 2.44, 3.65, and 3.25. Substance dependence was associated with higher odds of mood disorders than was abuse. Among the specific mood disorders, the increased odds of developing bipolar disorder were particularly high among individuals with drug dependence.

Conclusions

Individuals with adolescent and young adult-onset SUD had increased odds of developing a secondary mood disorder. This indicates that adolescents and young adults with SUD should be closely monitored for both positive and negative mood symptoms. SUD treatment and aftercare offer opportunities for the early identification of secondary mood disorders.     

The pattern of pharmacological treatment of bipolar patients discharged from psychiatric units in Poland

Background

The concomitant use of two or more mood stabilisers (MS), second-generation antipsychotics (SGA), lamotrigine as well as antidepressants, is frequently reported in the treatment of bipolar patients The aim of this study was to investigate the pattern of pharmacological treatment with special regard to polypharmacy defined as two or more psychiatric drugs taken at the same time in the same patients with bipolar disorder discharged from psychiatric units in Poland.

Combined effects of acute, very-low-dose ethanol and delta(9)-tetrahydrocannabinol in healthy human volunteers

Rationale

Previous studies examining the combined effects of ethanol and cannabis, or its primary psychoactive ingredient, ?⁹-tetrahydrocannabinol (THC), have provided mixed results. Data from an in vitro study suggests that combined, sub-threshold doses of these drugs may interact to produce synergistic effects. Very low doses of the two drugs in combination have not been tested in humans.

Materials and methods

This study assessed whether combinations of acute, very low doses of ethanol and THC produce synergistic effects on subjective, cognitive, and physiological measures. Healthy volunteers (n = 11) received capsules containing placebo or THC (2.5 mg), and beverages containing placebo or ethanol (0.1 and 0.2 g/kg) alone, and in combination, across separate sessions, in a within-subjects, randomized, double-blind design. During each session, participants completed measures of working memory, psychomotor ability, and simple reaction time, and provided subjective mood and drug effect ratings. Cardiovascular measures were obtained at regular intervals.

Results

As intended, when administered alone, these very low doses of ethanol and THC had only moderate effects on isolated measures. The combined effects of these drugs were not synergistic, and in some cases appeared to be less-than-additive.

Conclusions

Our data provide no evidence for synergistic effects of acute combinations of very-low-dose ethanol and THC on subjective or physiologic response, or on cognitive performance.     

Safety and efficacy of olanzapine monotherapy and olanzapine with a mood stabilizer in 18-week treatment of manic/mixed episodes for Japanese patients with bipolar I disorder

Abstract

Objective:

To assess the safety and efficacy of 18-week olanzapine monotherapy in Japanese patients with bipolar mania, following a 6-week, placebo- and haloperidol-controlled double-blind study (acute study). For those who discontinued the acute study due to lack of efficacy, safety and efficacy was assessed with a combination therapy of olanzapine and a mood stabilizer.     

The Wnt Pathway in Mood Disorders

Objectives:

To review the evidence of the involvement of the Wnt signalling pathway in mood disorders and in the action of drugs used to treat these disorders.

Methods:

We performed a careful PubMed search using as keywords all possible terms relevant to the Wnt pathway and crossing them with each of four areas, i.e., developmental effects, behavioural effects, mood disorders, and drugs used in their treatment. Papers were selected on the basis of their content and their data used for discussion.

Results:

Neurodevelopmental and behavioural data point to the possibility of involvement of the Wnt pathway in the pathophysiology of mood disorders. Clinical and post-mortem data are not sufficient to corroborate a definite role for Wnt alterations in any mood disorder. Combining genetic and pharmacological data, we may state that glycogen synthase kinase is the key molecule in bipolar disorder, as it is connected with many other signalling pathways that were shown to be involved in mood disorders, while Wnt molecules in the hippocampus appear to be mainly involved in depressive disorders.

Conclusions:

Altered Wnt signalling may play a role in the pathophysiology of mood disorders, although not a central one. It is premature to draw conclusions regarding the possible usefulness of Wnt manipulations in the treatment of mood disorders.     

Bayesian model of Hamilton Depression Rating Score (HDRS) with memantine augmentation in bipolar depression

Aim

Presynaptic and post‐synaptic glutamatergic modulation is associated with antidepressant activity that takes several weeks to reach a maximal full effect. Limiting mood elevating effects after single drug administration may be the result of compensatory synaptic processes. Therefore, using augmentation treatment with agents having presynaptic and post‐synaptic effects on the glutamatergic system, this study aims to evaluate the effect of augmentation therapy on the rate of change in mood elevation in patients with bipolar depression.

Methods

In a pilot study, 29 outpatients with bipolar depression on a stable lamotrigine dose regimen received placebo or memantine pills daily (titrated up by 5 mg week^–1 to 20 mg) in a randomized, double‐blind, parallel group, 8 week study. Patients were evaluated weekly using the 17‐item Hamilton Depression Rating Score (HDRS) and all data were analyzed simultaneously. Linear, exponential, maximal effect, Gompertz and inverse Bateman functions were evaluated using a Bayesian approach population pharmacodynamic model framework. In these models, differences in parameters were examined across the memantine and placebo augmentation groups.

Results

A Gompertz function with a treatment switch on the parameter describing the speed of HDRS decline (γ, 95% confidence interval [CI]) best described the data (γ_memantine = 1.8, 95% CI 0.9, 3.6), γ_placebo = 1.2, 95% CI 0.5, 3.5)). Between subject variability was identified on baseline HDRS (2.9, 95% CI 1.5, 4.4) and amplitude of score improvement (4.3, 95% CI 2.7, 6.5).

Conclusions

This pharmacodynamic approach identified an increased speed of response after memantine augmentation, compared with placebo augmentation in bipolar depression patients.     

Population screening of risky alcohol and drug use via Internet and Interactive Voice Response (IVR): a feasibility and psychometric study in a random sample

Background

The wide accessibility of computer-based technologies like the Internet and Interactive Voice Response (IVR) systems raises the question of whether population survey data could be collected more easily and cheaply compared to using paper questionnaires. In the area of possibly stigmatized behaviors such as problematic alcohol and drug use, the question extends to whether the prevalence of such behaviors in the general population could be surveyed without compromising the quality of the data.

Aims

This study compares Internet and IVR versions of the AUDIT and DUDIT with respect to: (1) response rate, (2) problematic alcohol and drug use and (3) reliability.

Method

5000 individuals, randomly selected from the Swedish general population, were contacted via postal mail and invited to complete the AUDIT and DUDIT questionnaires via Internet or IVR. In total, 1861 (37.8%) participated in the study, 1089 via Internet and 772 via IVR.

Results

The Internet administration mode yielded a higher response rate (38.1%) compared to the IVR mode (33.9%). When respondents were given a choice between Internet and IVR, a higher response rate resulted (43.2-46.6%). Problematic alcohol and drug use occurred among 21.1% and 2.8% of the sample, respectively, with no significant differences by administration mode. Both the AUDIT and DUDIT exhibited satisfactory reliability across administration modes, Cronbach's α 0.76/0.86.

Conclusions

Data quality does not deteriorate with computerized administration methods for the AUDIT and DUDIT in population studies but paper questionnaires should also be made available to respondents in order to maximize response rates.     

Clonazepam in the long-term treatment of patients with unipolar depression, bipolar and schizoaffective disorder.

The value of a long-term treatment with clonazepam in the prophylaxis of affective disorder is discussed controversially in the scientific literature. Altogether there are only a few reports on the use of this compound as a mood stabilizer, most of them describing patients suffering from bipolar affective disorder. The aim of this investigation was to evaluate clonazepam as a phase prophylactic medication in affective disorder. We conducted a retrospective chart review in 34 out-patients of our lithium clinic (15 suffering from unipolar depression, 15 from bipolar disorder, four from schizoaffective disorder), who had been treated with clonazepam as a long-term medication. Clonazepam was either given as monotherapy, or as in the case of lithium non-responders, as adjunctive therapy. Patients with unipolar depression had significantly (P=0.026) less depressive episodes after initiation of treatment with clonazepam. Patients with bipolar disorder did not benefit from this therapy. Neither manic/hypomanic phases nor depressive episodes were reduced in this group of patients. Interestingly, clonazepam also reduced affective phases in our four schizoaffective patients on a trend level. Our results indicate that patients with unipolar depression may benefit from a maintenance treatment with clonazepam. Due to methodological limitations our results need to be replicated in controlled double-blind randomized clinical trials.     

The reinforcing value of alcohol in a drinking to cope paradigm

Background

Alcohol use is often regarded as a means of coping with sadness and distress. The present research was conducted to explore the relation between negative mood and the reinforcing value of alcohol, while clarifying the role of coping motives.

Methods

Participants with a history of recent alcohol use (N = 44; 72% female) attended a laboratory session and were randomly assigned to either a negative (n = 22) or a neutral (n = 22) mood condition. A manipulation check confirmed that participants in the negative mood condition, but not the neutral mood condition, displayed a significant increase in negative affect. The multiple choice procedure (MCP) was used to measure the reinforcing value of alcohol after the mood manipulation.

Results

Regression models employing the MCP crossover point as the dependent variable and mood condition (neutral or negative) and drinking to cope as predictors indicated that a model with an interaction term accounted for the most variance.

Conclusions

These results suggest that the relation between mood and the reinforcing value of alcohol is moderated by drinking to cope, and help clarify the conditions under which drinking to cope may lead to negative outcomes.     

Smoking and everyday prospective memory: A comparison of self-report and objective methodologies

Aims

To examine whether persistent smoking leads to impairments in self-reported and objective measures of prospective memory (PM: the cognitive ability to remember to carry out activities at some future point in time).

Methods

An opportunity sample of 18 existing smokers and 22 who had never smoked were compared. An existing-groups design was utilised, comparing a smoking group with a never-smoked control group as the independent factor. Scores on the sub-scales of the Prospective and Retrospective Memory Questionnaire (PRMQ) and scores on the Cambridge Prospective Memory Test (CAMPROMPT) constituted the dependent factors. Age, mood, other drug use, strategy scores and IQ were also measured. Each participant was tested in a laboratory setting. Self-reported PM lapses were measured using the PRMQ. The CAMPROMPT was used as an objective measure of PM. Alcohol and other drug use were assessed by a Recreational Drug Use Questionnaire. The Hospital Anxiety and Depression Scale gauged levels of anxiety and depression. A strategy scale measured the number of strategies used to aid memory. The National Adult Reading Test measured IQ.

Results

After observing no between-group differences on age, mood, alcohol use, strategy use, and IQ, smokers and the never-smoked did not differ on the self-reported lapses measured on the PRMQ. However, smokers recalled significantly fewer items on the CAMPROMPT than the never-smoked group.

Conclusion

The results of the present study suggest that persistent smoking leads to impairments in everyday PM.     

Biomarkers in cerebrospinal fluid of patients with bipolar disorder versus healthy individuals: A systematic review

Background

The pathophysiological processes of bipolar disorder (BD) may be detectable by the use of cerebrospinal fluid (CSF) biomarkers.

Opioid maintenance patients with QTc prolongation: Congenital long QT syndrome mutation may be a contributing risk factor

Objectives

This study investigates opioid maintenance treatment (OMT) patients found to have corrected QT (QTc) interval above 500 ms, with particular focus on past medical history, genetic testing and cardiac investigations.

Methods

Detailed medical and cardiac history was obtained, with particular focus upon risk factors. Cardiac investigations, including genetic testing for the five most common long QT syndrome (LQTS) mutations, exercise electrocardiography (ECG) and 24-h ECG recordings, were performed.

Results

Of 200 OMT patients assessed with ECG, seven methadone maintained patients identified with QTc interval above 500 ms participated in this study. Two were identified as heterozygous LQTS mutation carriers. Both had experienced cardiac symptoms prior to and during OMT. No other risk factors for QTc prolongation were detected among the seven patients. Six of the seven patients underwent further cardiac investigations. QTc intervals fluctuated widely over 24 h and during exercise for all patients. Only one of the LQTS mutation carriers switched to buprenorphine and started on a beta-blocker. Despite strong medical advice and information, none of the other patients wanted to switch to buprenorphine or take other cardiac protective measures.

Conclusion

Findings indicate the importance of recording a thorough past medical history, focusing specifically on previous cardiac symptoms, and on other known risk factors for QTc prolongation, prior to initiating patients on methadone.     

Adjunctive antidepressants in bipolar depression: A cohort study of six- and twelve-months rehospitalization rates

Although antidepressants (ADs) are widely used in bipolar depression, there is weak evidence for their effectiveness and safety in this condition. Furthermore, there is a paucity of studies on the risk-benefit ratio of AD maintenance treatment in bipolar disorder (BD). We compared rehospitalization rates of patients with BD-I depressive episode who were discharged with mood stabilizers (MSs) and/or atypical antipsychotics (AAPs) with or without adjunctive AD. Ninety-eight patients with BD-I who were hospitalized with a depressive episode between 2005 and 2013 were retrospectively followed for 6-months and 1-year rehospitalization rates, as well as time to rehospitalization, according to treatment at discharge: MSs and/or AAPs with or without AD. Multivariable survival models adjusted for covariates known to influence rehospitalization were conducted. Six-months and 1-year rehospitalization rates were significantly lower in the adjunctive-AD treatment group compared to the no-AD group (9.2% vs. 36.4%, P = .001, power = 0.87 and 12.3% vs. 42.4%, P = .001, power = 0.89, respectively). Time to rehospitalization within 6-months and 1-year was significantly longer in the adjunctive-AD treatment group (169.9 vs 141 days, P = .001 and 335.6 vs 252.3 days, P = .001, respectively). Adjunctive-AD treatment at discharge reduced significantly the adjusted risk of rehospitalization within 6-months (HR = 0.081, 95% CI: 0.016–0.412, P = 0.002) and 1-year (HR = 0.149, 95% CI: 0.041–0.536, P = 0.004). Moreover, adjunctive-AD treatment did not increase rehospitalization rates of manic episode. In conclusion, adjunctive-AD therapy to MS/AAP at discharge from BD-I depressive episode hospitalization is associated with a lower rate of and a longer time to rehospitalization during a 1-year follow up period.