Electroconvulsive Therapy (ECT) in Bipolar Disorder Patients with Ultra-Rapid Cycling and Unstable Mixed States.

Background and Objectives: Unstable mixed episodes or rapid switching between opposite affective poles within the scope of short cycles was first characterized in 1967 by S. Mentzos as complex polymorphous states with chaotic overlap of manic and depressive symptoms. Well-known examples include antidepressant-induced mania/hypomania and rapid/ultra-rapid/ultradian cycling, when clinicians observe an almost continuous mixed state with a constant change of preponderance of manic or depressive symptoms. Achieving stable remission in these cases is challenging with almost no data on evidence-based treatment. When mood stabilizers are ineffective, electroconvulsive therapy (ECT) has been suggested. Objectives: After reviewing the evidence from available literature, this article presents our own clinical experience of ECT efficacy and tolerability in patients with ultra-rapid cycling bipolar disorder (BD) and unstable mixed states. Materials and Methods: We conducted an open, one-year observational prospective study with a "mirror image" design, including 30 patients with rapid and ultra-rapid cycling BD on long-term mood stabilizer treatment (18 received lithium carbonate, 6 on valproate and 6 on carbamazepine) with limited effectiveness. A bilateral ECT course (5-10 sessions) was prescribed for regaining mood stability. Results: ECT was very effective in 12 patients (40%) with a history of ineffective mood stabilizer treatment who achieved and maintained remission; all of them received lithium except for 1 patient who received carbamazepine and 2 with valproate. Nine patients (30%) showed partial response (one on carbamazepine and two on valproate) and nine patients (30%) had no improvement at all (four on carbamazepine and two on valproate). For the whole sample, the duration of affective episodes was significantly reduced from 36.05 ± 4.32 weeks in the year prior to ECT to 21.74 ± 12.14 weeks in the year post-ECT (p < 0.001). Depressive episodes with mixed and/or catatonic features according to DSM-5 specifiers were associated with a better acute ECT response and/or long-term mood stabilizer treatment outcome after ECT. Conclusions: ECT could be considered as a useful option for getting mood instability under control in rapid and ultra-rapid cycling bipolar patients. Further randomized trials are needed to confirm these results.

Bipolar Disorder and Comorbid Use of Illicit Substances.

Substance use disorders (SUD) are highly prevalent in bipolar disorder (BD) and significantly affect clinical outcomes. Incidence and management of illicit drug use differ from alcohol use disorders, nicotine use of behavioral addictions. It is not yet clear why people with bipolar disorder are at higher risk of addictive disorders, but recent data suggest common neurobiological and genetic underpinnings and epigenetic alterations. In the absence of specific diagnostic instruments, the clinical interview is conducive for the diagnosis. Treating SUD in bipolar disorder requires a comprehensive and multidisciplinary approach. Most treatment trials focus on single drugs, such as cannabis alone or in combination with alcohol, cocaine, or amphetamines. Synopsis of data provides limited evidence that lithium and valproate are effective for the treatment of mood symptoms in cannabis users and may reduce substance use. Furthermore, the neuroprotective agent citicoline may reduce cocaine consumption in BD subjects. However, many of the available studies had an open-label design and were of modest to small sample size. The very few available psychotherapeutic trials indicate no significant differences in outcomes between BD with or without SUD. Although SUD is one of the most important comorbidities in BD with a significant influence on clinical outcome, there is still a lack both of basic research and clinical trials, allowing for evidence-based and specific best practices.

Classical Risk Factors and Inflammatory Biomarkers: One of the Missing Biological Links between Cardiovascular Disease and Major Depressive Disorder.

BACKGROUND: Cardiovascular disorders (CVD) and major depressive disorder (MDD) are the most frequent diseases worldwide responsible for premature death and disability. Behavioral and immunological variables influence the pathophysiology of both disorders. We therefore determined frequency and severity of MDD in CVD and studied whether MDD without CVD or other somatic diseases influences classical and inflammatory biomarkers of cardiovascular risk. In addition, we investigated the influence of proinflammatory cytokines on antidepressant treatment outcome. METHODS: In a case-control design, 310 adults (MDD patients without CVD, CVD patients, and cardiologically and psychiatrically healthy matched controls) were investigated. MDD patients were recruited after admission in a psychiatric university hospital. Primary outcome criteria were clinical depression ratings (HAM-D scale), vital signs, classical cardiovascular risk factors and inflammatory biomarkers which were compared between MDD patients and healthy controls. RESULTS: We detected an enhanced cardiovascular risk in MDD. Untreated prehypertension and signs directing to a metabolic syndrome were detected in MDD. Significantly higher inflammatory biomarkers such as the high sensitivity C-reaktive protein (hsCRP) and proinflammatory acute phase cytokines interleukine-1ß (IL-1ß) and interleukine-6 (IL-6) underlined the higher cardiovascular risk in physically healthy MDD patients. Surprisingly, high inflammation markers before treatment were associated with better clinical outcome and faster remission. The rate of MDD in CVD patients was high. CONCLUSIONS: Patients suffering from MDD are at specific risk for CVD. Precise detection of cardiovascular risks in MDD beyond classical risk factors is warranted to allow effective prophylaxis and treatment of both conditions. Future studies of prophylactic interventions may help to provide a basis for prophylactic treatment of both MDD and CVD. In addition, the high risk for MDD in CVD patients was confirmed and underlines the requirement for clinical attention.

[Lithium treatment in patients with impaired kidney function: Between Scylla and Charybdis]. / Lithiumtherapie bei eingeschränkter Nierenfunktion: Zwischen Skylla und Charybdis.

Introduction In quite a few patients with bipolar disorder there is no real alternative to lithium treatment despite impaired kidney function. Is it possible to continue lithium treatment despite kidney malfunction by changing dosage and/or frequency of administration? Case Report We report on a 65-year-old woman suffering from bipolar-I disorder who had been on lithium treatment for many decades. While on lithium, the glomerular filtration rate (GFR) decreased constantly. A decision had to be made whether to switch to a more tolerable o.d. administration or to taper off lithium. Conclusion With a single dose at bedtime, the serum levels remained stable; however, kidney function unfortunately did not improve. A relevant increase of GFR above the level of 60 mL/min/1,73 m2 was only achieved after a 50% dose reduction leading also to a substantial decrease of lithium serum levels. A kidney protective lithium application in patients with reduced renal function is like sailing between Scylla and Charybdis.

First results of a refeeding program in a psychiatric intensive care unit for patients with extreme anorexia nervosa.

BACKGROUND: Anorexia nervosa (AN) is associated with a high mortality rate. This study describes a compulsory re-feeding program established in Munich for extremely underweight patients. METHODS: The contract between the patient and the therapeutic team included mandatory inpatient status, establishment of guardianship and compulsory re-feeding with a percutaneous gastric feeding tube, as indicated. The predefined target was a body mass index (BMI) of 17 kg/m(2). Data on the first 68 patients with AN are presented. RESULTS: 65 (95.6%) patients were female and mean age at admission was 26.5 ± 8.5 years. BMI increased from 12.3 ± 1.4 kg/m(2) at admission to 16.7 ± 1.7 kg/m(2) at discharge. Thirty-two (47.1%) patients had the restrictive subtype (ANR) and 36 (52.9%) had the binging and purging subtype (ANBP). Duration of illness before admission (p = .004), days of treatment until discharge (p = .001) and weight increase (p = .02) were significantly different between subgroups in favor of patients with ANR. Also, seasonal differences could be found. Comparison of feeding methods showed that percutaneous tube feeding was superior. Almost half of the patients were treated with psychotropic medication. To date, however, the number of patients included in this program is too small to assess rare complications of this acute treatment program and long term outcomes of AN. CONCLUSIONS: An intensive care program for severely ill AN patients has been successfully established. Besides averting physical harm in the short term, this program was designed to enable these patients to participate in more sophisticated psychotherapeutic programs afterwards. To our knowledge, this is the first such program that regularly uses percutaneous feeding tubes.

Saving time and money: a validation of the self ratings on the prospective NIMH Life-Chart Method (NIMH-LCM).

BACKGROUND: Careful observation of the longitudinal course of bipolar disorders is pivotal to finding optimal treatments and improving outcome. A useful tool is the daily prospective Life-Chart Method, developed by the National Institute of Mental Health. However, it remains unclear whether the patient version is as valid as the clinician version. METHODS: We compared the patient-rated version of the Lifechart (LC-self) with the Young-Mania-Rating Scale (YMRS), Inventory of Depressive Symptoms-Clinician version (IDS-C), and Clinical Global Impression-Bipolar version (CGI-BP) in 108 bipolar I and II patients who participated in the Naturalistic Follow-up Study (NFS) of the German centres of the Bipolar Collaborative Network (BCN; formerly Stanley Foundation Bipolar Network). For statistical evaluation, levels of severity of mood states on the Lifechart were transformed numerically and comparison with affective scales was performed using chi-square and t tests. For testing correlations Pearson´s coefficient was calculated. RESULTS: Ratings for depression of LC-self and total scores of IDS-C were found to be highly correlated (Pearson coefficient r = -.718; p < .001), whilst the correlation of ratings for mania with YMRS compared to LC-self were slightly less robust (Pearson coefficient r = .491; p = .001). These results were confirmed by good correlations between the CGI-BP IA (mania), IB (depression) and IC (overall mood state) and the LC-self ratings (Pearson coefficient r = .488, r = .721 and r = .65, respectively; all p < .001). CONCLUSIONS: The LC-self shows a significant correlation and good concordance with standard cross sectional affective rating scales, suggesting that the LC-self is a valid and time and money saving alternative to the clinician-rated version which should be incorporated in future clinical research in bipolar disorder. Generalizability of the results is limited by the selection of highly motivated patients in specialized bipolar centres and by the open design of the study.

Bipolar disorders and schizophrenia: discrete disorders?

Background: With similarities in heritability, neurobiology and symptomatology, the question has been raised whether schizophrenia and bipolar disorder are truly distinctive disorders or belong to a continuum. This narrative review summarizes common and distinctive findings from genetics, neuroimaging, cognition and clinical course that may help to solve this ethiopathogenetic puzzle. Methods: The authors conducted a literature search for papers listed in PubMed and Google Scholar, using the search terms "schizophrenia" and "bipolar disorder" combined with different terms such as "genes", "neuroimaging studies", "phenomenology differences", "cognition", "epidemiology". Articles were considered for inclusion if they were written in English or Spanish, published as full articles, if they compared subjects with schizophrenia and bipolar disorder, or subjects with either disorder with healthy controls, addressing differences between groups. Results: Several findings support the hypothesis that schizophrenia and bipolar disorder are discrete disorders, yet some overlapping of findings exists. The evidence for heritability of both SZ and BD is obvious, as well as the environmental impact on individual manifestations of both disorders. Neuroimaging studies support subtle differences between disorders, it appears to be rather a pattern of irregularities than an unequivocally unique finding distinguishing schizophrenia from bipolar disorder. The cognitive profile displays differences between disorders in certain domains, such as premorbid intellectual functioning and executive functions. Finally, the timing and trajectory of cognitive impairment in both disorders also differs. Conclusion: The question whether SZ and BD belong to a continuum or are separate disorders remains a challenge for further research. Currently, our research tools may be not precise enough to carve out distinctive, unique and undisputable differences between SZ and BD, but current evidence favors separate disorders. Given that differences are subtle, a way to overcome diagnostic uncertainties in the future could be the application of artificial intelligence based on BigData. Limitations: Despite the detailed search, this article is not a full and complete review of all available studies on the topic. The search and selection of papers was also limited to articles in English and Spanish. Selection of papers and conclusions may be biased by the personal view and clinical experience of the authors.

The detrimental effects of smoking on the course and outcome in adults with bipolar disorder-A narrative review.

Background: Smoking is a substantial and avoidable risk for physical disability and premature death. Despite a declining tobacco use in the community of developed countries, smoking remains abundant in people with mental disorders. This narrative review highlights the epidemiology, consequences and treatment options of tobacco use disorder (TUD) and nicotine dependence (ND) in people with bipolar disorder (BD). Methods: The authors conducted a Medline literature search from 1970 to November 2022 using MeSH terms "bipolar disorder" x "smoking" or "nicotine" or "tobacco" that retrieved 770 results. Search results were complemented by additional literature retrieved from examining cross references and by hand search in text books. Finally, 92 references were considered as essential and selected for the educational purpose of this review. Summary of findings: Lifetime and point prevalence of smoking in people with BD is in the range of 45-70% and thus about 2-3 times more frequent in BD than in community samples. Smoking, TUD and ND have a detrimental impact both on mental and physical health as well as mortality in people with BD. In the absence of large controlled studies in comorbid BD and TUD or ND, pharmacological treatment follows the individual guidance for each disorder. Community-based psychosocial interventions for TUD and ND appear to be suitable in people with BD, too, as well as Cognitive Behavioral (CBT) or Acceptance and Commitment (ACT) based psychotherapies. Conclusions: Smoking is a modifiable risk factor causing increased risks both for mental and physical health in BD, and deserves more attention in treatment. More treatment research into pharmacological and psychosocial interventions in comorbid BD and TUD or ND are still needed to deliver evidence-based recommendations to physicians.

Reducing Addiction in Bipolar Disorder via Hacking the Dopaminergic System.

The dopaminergic system plays a central and decisive role in substance use disorder (SUD), bipolar disorder (BD), and possibly in a subgroup of patients with refractory depression. Common genetic markers and underlying cellular processes, such as kindling, support the close link between these disorders, which is also expressed by the high rate of comorbidity. Although partial dopamine agonists/antagonists acting on D2 and D3 receptors have an established role in treating BD, their usefulness in SUD is less clear. However, dopamine D3 receptors were shown to play a central role in SUD and BD, making D2/D3 partial agonists/antagonists a potential target for both disorders. This narrative review examines whether these substances bear the promise of a future therapeutic approach especially in patients with comorbid BD and SUD.

Comorbid Bipolar and Alcohol Use Disorder-A Therapeutic Challenge.

Comorbidity rates in Bipolar disorder rank highest among major mental disorders, especially comorbid substance use. Besides cannabis, alcohol is the most frequent substance of abuse as it is societally accepted and can be purchased and consumed legally. Estimates for lifetime comorbidity of bipolar disorder and alcohol use disorder are substantial and in the range of 40-70%, both for Bipolar I and II disorder, and with male preponderance. Alcohol use disorder and bipolarity significantly influence each other's severity and prognosis with a more complicated course of both disorders. Modern treatment concepts acknowledge the interplay between these disorders using an integrated therapy approach where both disorders are tackled in the same setting by a multi-professional team. Motivational interviewing, cognitive behavioral and socio- therapies incorporating the family and social environment are cornerstones in psychotherapy whereas the accompanying pharmacological treatment aims to reduce craving and to optimize mood stability. Adding valproate to lithium may reduce alcohol consumption whereas studies with antipsychotics or naltrexone and acamprosate did not affect mood fluctuations or drinking patterns. In summary, there is a continuous need for more research in order to develop evidence-based approaches for integrated treatment of this frequent comorbidity.

How Does Adding the DSM-5 Criterion Increased Energy/Activity for Mania Change the Bipolar Landscape?

According to DSM-IV, the criterion (A) for diagnosing hypomanic/manic episodes is mood change (i.e., elevated, expansive or irritable mood). Criterion (A) was redefined in DSM-5 in 2013, adding increased energy/activity in addition to mood change. This paper examines a potential change of prevalence data for bipolar I or II when adding increased energy/activity to the criterion (A) for the diagnosis of hypomania/mania. Own research suggests that the prevalence of manic/hypomanic episodes drops by at least one third when using DSM-5 criteria. Whether this has positive or negative impact on clinical practice and research still needs further evaluation.

Mania and bipolar depression: complementing not opposing poles-a post-hoc analysis of mixed features in manic and hypomanic episodes.

BACKGROUND: Depending on the classification system used, 5-40% of manic subjects present with concomitant depressive symptoms. This post-hoc analysis evaluates the hypothesis that (hypo)manic subjects have a higher burden of depression than non-(hypo)manic subjects. METHODS: Data from 806 Bipolar I or II participants of the Stanley Foundation Bipolar Network (SFBN) were analyzed, comprising 17,937 visits. A split data approach was used to separate evaluation and verification in independent samples. For verification of our hypotheses, we compared mean IDS-C scores ratings of non-manic, hypomanic and manic patients. Data were stored on an SQL-server and extracted using standard SQL functions. Linear correlation coefficients and pivotal tables were used to characterize patient groups. RESULTS: Mean age of participants was 40 ± 12 years (range 18-81). 460 patients (57.1%) were female and 624 were diagnosed as having bipolar I disorder (77.4%) and 182 with bipolar II (22.6%). Data of 17,937 visits were available for analyses, split into odd and even patient numbers and stratified into three groups by YMRS-scores: not manic < 12, hypomanic < 21, manic < 30. Average IDS-C sum scores in manic or hypomanic states were significantly higher (p < .001) than for non-manic states. (Hypo)manic female patients were likely to show more depressive symptoms than males (p < .001). Similar results were obtained when only the core items of the YMRS or only the number of depressive symptoms were considered. Analyzing the frequency of (hypo)manic mixed states applying a proxy of the DSM-5 mixed features specifier extracted from the IDS-C, we found that almost 50% of the (hypo)manic group visits fulfilled DSM-5 mixed features specifier criteria. CONCLUSION: Subjects with a higher manic symptom load are also significantly more likely to experience a higher number of depressive symptoms. Mania and depression are not opposing poles of bipolarity but complement each other.

Aripiprazole as adjunct to a mood stabilizer and citalopram in bipolar depression: a randomized placebo-controlled pilot study.

OBJECTIVE: The use of atypical antipsychotics (AAPs) for the treatment of unipolar and bipolar depression has been more and more frequently evaluated, and aripiprazole showed positive effects in the treatment of unipolar depression. However, no placebo-controlled studies of adjunctive aripiprazole for the treatment of bipolar depression have been performed yet. METHODS: In this prospective, double-blind, placebo-controlled, randomized trial, 23 inpatients with bipolar depression according to DSM-IV criteria were included. Before randomization, patients had to be on a constant mood stabilizer treatment with lithium or valproate for at least 1 week. After inclusion, all patients were openly treated with additional citalopram and with additional aripiprazole or placebo for 6 weeks. The primary outcome parameter was the reduction in depressive symptoms according to the Hamilton Depression Rating Scale (HDRS) within 6 weeks. RESULTS: After 6 weeks of treatment, the HDRS score decreased in both groups. There was no significant difference between both the groups at any point of time with respect to the HDRS. CONCLUSIONS: Derived from this small pilot study, adjunctive aripiprazole does not seem to be a promising strategy for the acute treatment of bipolar depression. However, this lack of additional benefit seems to stem from the already good effectiveness of the control group, namely the treatment with citalopram.

The Impact of Subsyndromal Bipolar Symptoms on Patient's Functionality and Quality of Life.

Subsyndromal symptoms have rarely been in the focus of bipolar research. This may be, in part, due to the fact that there is neither a uniform definition nor do they constitute an indication of regulatory and commercial interest. Nevertheless, they do have a decisive impact on the long-term course of bipolar disorder (BD), and the degree of functionality and quality of life (QoL) is more likely determined by their presence or absence than by acute episodes. Summarizing the literature an estimated 20-50% of patients suffer inter-episodically or chronically from subsyndromal BD. The most prominent symptoms that interfere with functionality are subsyndromal depression, disturbances of sleep, and perceived cognitive impairment, whereas anxiety negatively impacts on QoL. In the absence of evidence-based pharmacological treatments for subsyndromal BD, clinical practice adopts guidelines designed for treatment-resistant full-blown episodes of BD, supplemented by cognitive-behavioral, family focused or social-rhythm-based psychotherapies.

[The relevance of dopamine agonists in the treatment of depression]. / Die Bedeutung von Dopaminagonisten in der Behandlung der Depression.

The pathophysiology of depression has been assigned to the noradrenalin and serotonin system. Results of different studies also support a role of the dopaminergic system in depression: In particular, psychomotor retarded depressive patients exhibited lower levels of homovanillic acid (metabolite of dopamine). While the moodimproving effect of methylphenidat, D-amphetamine and cocaine is also supportive for an involvement of the dopaminergic system, reserpine leads to diminished dopamine levels and may induce a depressive syndrome as well as dopamine receptor-blockers. Dopamine-mediated motor disturbances and accompanying changes in mood in Parkinson's disease likewise support pathophysiological similarities of depression and Parkinson's disease. Psychomotor inhibition, reduced facial expression and decreased speech production in depression are in line with a hypodopaminergic state of the respective motor areas. There is evidence from open studies for the ergotalkaloids bromocriptine and pergolide to have anti-depressive effects. Controlled studies for the selective dopamine D2/D3-agonists pramipexole and ropinirole are existing. Bupropion, a selective dopamine and noradrenaline reuptake inhibitor (DNRI), has proven antidepressant efficacy in controlled studies and has been licensed for the treatment of depression.

Efficacy of quetiapine monotherapy in rapid-cycling bipolar disorder in comparison with sodium valproate.

BACKGROUND: Rapid-cycling bipolar disorder is often characterized by a lack of response to psychopharmacological treatment, and a standard therapy has not been developed yet. The aim of this study was to examine the long-term efficacy and safety of a monotherapy with quetiapine or sodium valproate (VPA) in patients with rapid-cycling bipolar disorder. METHODS: This open-label, randomized, parallel group monotherapy pilot study was conducted at 3 German centers. A sample of 38 remitted or partly remitted patients with bipolar disorder and rapid cycling (quetiapine n = 22; VPA n = 16) were treated with quetiapine or VPA (flexible dose design) for 12 months. RESULTS: Forty-one percent of the patients with quetiapine and 50% with VPA completed the trial. On the basis of ITT-LOCF, Life Chart Method data showed that patients being treated with quetiapine had significantly less moderate to severe depressive days than patients on VPA (mean +/- SD, 11.7 +/- 16.9 days vs 27.7 +/- 24.9 days; P = 0.04) while they did not differ in the number of days with manic or hypomanic symptoms. Furthermore, according to the Clinical Global Impression Scale, bipolar version, the responder rates tended to be higher for quetiapine than for VPA. There were no differences found evaluating the Hamilton Depression Rating Scale, the Montgomery-Asberg Depression Scale, and the Young Mania Rating Scale. The incidence of adverse events, especially of orthostatic dysregulation, sedation, and weight gain, was significantly higher in the quetiapine group. CONCLUSIONS: In this study, quetiapine was more effective than VPA on the number of depressive days and similar to VPA in the treatment of manic symptoms. Quetiapine was associated with a greater incidence of side effects, particularly orthostatic dysregulation, sedation, and weight gain.

[Speed of onset of depressive episodes: a clinical criterion helpful for separating uni- from bipolar affective disorders]. / Geschwindigkeit des Depressionsbeginns: Ein Unterscheidungsmerkmal hinsichtlich uni- versus bipolarer affektiver Störungen.

OBJECTIVE: Depressive episodes can begin abruptly or start very slowly (over weeks). This relevant clinical feature of affective disorders has not been systematically investigated so far. The aim of this study was to analyze speed of onset of depressive episodes in patients with unipolar depression (UD) and bipolar affective disorders (BD). METHODS: 158 adult patients with UD (N = 108) and BD (N = 50) were examined using the structured "Onset-of-Depression Inventory". Only patients without acute critical life events preceding the onset were included in the study. RESULTS: There was a significant positive correlation between speed of onset of the present and that of the preceding depressive episode (rho = 0.66; p < 0.001). The association between speed of onset and speed of decay of depressive episodes failed to be significant (rho = 0.20; p = 0.09). Patients with bipolar disorder were found to develop depressive episodes significantly faster than patients with major depression (p < 0.001): Whereas depressive episodes started in 58% of patients with bipolar disorder within one week, this was only the case in 7.4% of patients with major depression. CONCLUSIONS: Within subjects, the speed of onset of depression is similar across different episodes. In the absence of acute critical life events, rapid onset of depressive episodes (within one week) is typical for bipolar depression, but not for unipolar depression. A rapid onset of depressive episodes might point to BD in patients with solely depressive episodes in the past and to subgroups with different neurobiological pathogenetic mechanisms.

Mirtazapine monotherapy versus combination therapy with mirtazapine and aripiprazole in depressed patients without psychotic features: a 4-week open-label parallel-group study.

BACKGROUND: There is preliminary evidence that the atypical antipsychotic aripiprazole, which is a partial agonist at D(2) and 5-HT(1A) receptors and a potent antagonist at 5-HT(2A) receptors, may be useful as an augmentation strategy in treatment-resistant depression. METHOD: In this 4-week open-label non-randomized parallel-group study, the safety and efficacy of aripiprazole as add-on treatment strategy in patients suffering from non-delusional depression was investigated. Forty drug-free depressed inpatients without psychotic symptoms (13 men, 27 women), suffering from a major depressive episode or bipolar disorder, depressive state (DSM-IV criteria), were included in the study. The patients were treated either with mirtazapine monotherapy (45 mg/day) or combination therapy (mirtazapine 45 mg/day plus aripiprazole 15 mg/day) for 4 weeks. Safety and efficacy were assessed weekly using the Hamilton Depression Rating Scale, the Simpson-Angus Scale and the Barnes Akathisia Scale. RESULTS: Mirtazapine monotherapy and combined treatment with mirtazapine and aripiprazole showed comparable antidepressant effects as assessed at the endpoint of the study period. However, additional administration of aripiprazole accelerated the onset of antidepressant action in patients suffering from treatment-resistant depression. Additive use of aripiprazole reduced the mirtazapine-induced increase in the body mass index. Moreover, mirtazapine had favourable effects on aripiprazole-induced akathisia. No other extrapyramidal side effects were seen in the combination therapy group. CONCLUSION: Combined therapy with mirtazapine and aripiprazole is a safe and well-tolerated treatment option which may be useful especially in treatment-resistant depression. Double-blind controlled studies are needed to further explore the efficacy and safety of aripiprazole in depressed patients.

Impact of cognitive-psychoeducational interventions in bipolar patients and their relatives.

BACKGROUND: In recent years, several controlled studies could show that psychoeducational interventions have been effective for relapse prevention in bipolar disorders. We therefore established a cognitive-psychoeducational group intervention with 14 sessions providing information about the illness, early warning signs, cognitive and behavioural strategies for stress management and social rhythm. Additionally we offered a group intervention for the patients' relatives. The objective of this study was to describe the outcome associated with our psychoeducational intervention in bipolar patients and their relatives. METHODS: Sixty-two bipolar patients attended 14 sessions (à 90 min) of cognitive-psychoeducational group therapy. Patients' knowledge of bipolar disorder and their satisfaction with the treatment were assessed using self-developed questionnaires before and after the group intervention. Additionally, 49 relatives of bipolar patients received two psychoeducational workshops of 4 hours each. We assessed demographic variables, burden, high expressed emotion and depressive symptoms of the relatives before and after the two workshops and at 1-year follow-up. RESULTS: Patients significantly improved their knowledge of bipolar disorder. They also have benefited from the discussions and the exchange of useful coping strategies. Burden and high expressed emotions showed no significant reductions at post-assessment, however they were significantly reduced at 1-year follow-up. Relatives also felt significantly better informed about the illness. CONCLUSIONS: These findings show that psychoeducational interventions in bipolar patients and their relatives improve patients' and their relatives' knowledge of the illness and the burden of the disorder as well as high expressed emotions are reduced in relatives at 1-year follow-up.