Manic Phase Of Bipolar Disorder Research Articles

The Effect of Mental Illness on Language Regression to the Mother Tongue in Bilingual Teenagers

The Effect of Mental Illness on Language Regression to the Mother Tongue in Bilingual Teenagers

Oral Divalproex Sodium Loading for Adolescent Outpatients With Acute Mania/Hypomania

Article AbstractLetter to the Editor Sir: Treatment with divalproex sodium delayed release (DR)of the manic phase of bipolar disorder in adults results in rapidclinical response after a therapeutic serum concentration of 50µg/mL is achieved. When divalproex treatment was initiated at750 mg/day and daily dosage was subsequently titrated on thebasis of serial serum divalproex sodium concentration determinations(i.e., a standard titration approach), therapeutic levelsand corresponding antimanic response were observed in mostpatients after 5 to 10 days. In contrast, an oral loading strategyof divalproex sodium 20 mg/kg/day produces serum valproicacid concentrations of approximately 80 µg/mL after 1 to 2 daysof treatment.

Event Related Oscillatory Activity in Euthymic and Manic Phases of Bipolar Disorder

Event Abstract Back to Event Event Related Oscillatory Activity in Euthymic and Manic Phases of Bipolar Disorder Aysegul Ozerdem1, 2, 3*, B. Güntekin4, Z. Tunca1 and Erol Basar4 1 Dokuz Eylül University Medical School, Department of Psychiatry, Turkey 2 Dokuz Eylül University Health Sciences Institute, Department of Neurosciences, Turkey 3 Dokuz Eylül University, Turkey 4 İstanbul Kültür University, Turkey Objectives: We aimed to detect oscillatory responses and effect of valproate, a mood stabilizer with GABA/Glutamate modulating and neuroprotective effect on the oscillatory activity in patients with bipolar disorder. Methods: Twenty medication free, manic (n=10) or euthymic (n=10) bipolar patients and 20 sex and age matched healthy controls were enrolled in the study. In the patient group, event related potentials (ERPs) to target stimuli in visual odd-ball paradigm was measured before and after six weeks of valproate monotherapy. Same measurement was done twice with six week difference in the healthy controls. Different frequency band responses were obtained by digital filtration of ERPs. Repeated measures and one-way ANOVA, Wilcoxon and Mann Whitney U tests were used. Results: Manic patients showed significantly higher baseline occipital beta (18-30 Hz) (p: 0.014) response than healthy controls and did not have the occipito-frontal alpha (8-13 Hz) dominance presented by the control group. Occipital beta response reduced significantly (p: 0.009) and became similar to controls after treatment. Post-treatment alpha responses were significantly lower than baseline in anterior temporal (p: 0.038) and occipital (p: 0.027) locations. Healthy controls displayed a significantly increased frontal alpha response at the second assessment but the patients did not. Euthymic patients showed significantly higher baseline delta response compared to healthy controls in the left frontal location (p: =0.03). After valproate, delta responses in Fz (p: 0.04) F3 (p: 0.03), and temporal T3 (p: 0.02), T4 (p: 0.01), T5 (p: 0.01) channels decreased compared to baseline Conclusions: Bipolar patients show different patterns of disturbed oscillatory activity at different phases of the illness on which valproate seems to have a selectively corrective effect. This may be through modulation of GABA/glutamate and indicative of medication's neuroprotective effect. Conference: 10th International Conference on Cognitive Neuroscience, Bodrum, Turkey, 1 Sep - 5 Sep, 2008. Presentation Type: Oral Presentation Topic: Symposium 9: Cognitive electrophysiology in neuropsychriatric disorders Citation: Ozerdem A, Güntekin B, Tunca Z and Basar E (2008). Event Related Oscillatory Activity in Euthymic and Manic Phases of Bipolar Disorder. Conference Abstract: 10th International Conference on Cognitive Neuroscience. doi: 10.3389/conf.neuro.09.2009.01.042 Copyright: The abstracts in this collection have not been subject to any Frontiers peer review or checks, and are not endorsed by Frontiers. They are made available through the Frontiers publishing platform as a service to conference organizers and presenters. The copyright in the individual abstracts is owned by the author of each abstract or his/her employer unless otherwise stated. Each abstract, as well as the collection of abstracts, are published under a Creative Commons CC-BY 4.0 (attribution) licence (https://creativecommons.org/licenses/by/4.0/) and may thus be reproduced, translated, adapted and be the subject of derivative works provided the authors and Frontiers are attributed. For Frontiers’ terms and conditions please see https://www.frontiersin.org/legal/terms-and-conditions. Received: 27 Nov 2008; Published Online: 27 Nov 2008. * Correspondence: Aysegul Ozerdem, Dokuz Eylül University Medical School, Department of Psychiatry, Izmir, Turkey, aysegul.ozerdem@deu.edu.tr Login Required This action requires you to be registered with Frontiers and logged in. To register or login click here. Abstract Info Abstract The Authors in Frontiers Aysegul Ozerdem B. Güntekin Z. Tunca Erol Basar Google Aysegul Ozerdem B. Güntekin Z. Tunca Erol Basar Google Scholar Aysegul Ozerdem B. Güntekin Z. Tunca Erol Basar PubMed Aysegul Ozerdem B. Güntekin Z. Tunca Erol Basar Related Article in Frontiers Google Scholar PubMed Abstract Close Back to top Javascript is disabled. Please enable Javascript in your browser settings in order to see all the content on this page.

Ziprasidone: clinical properties and therapeutic promise

Ziprasidone is a second-generation antipsychotic with combined dopamine and serotonin receptor antagonistic activity. The initial evidence suggests an effective dosage range of 120–160 mg/day. Clinical trials have demonstrated that the drug is an effective antipsychotic in schizophrenia and schizoaffective disorders with some beneficial effect on negative symptoms and on symptoms of depression in schizophrenia. In addition, ziprasidone is efficacious in the manic phase of bipolar disorder. Ziprasidone has relatively few side effects, while its efficacy for florid positive symptoms is at least equivalent to conventional antipsychotics. The main adverse effects are somnolence and nausea. It has a better effect on cognitive deficiencies than conventional antipsychotics. The almost complete lack of weight gain or metabolic side effects makes ziprasidone an attractive second-generation antipsychotic agent.

The effects of pentazocine, a kappa agonist, in patients with mania

Past evidence suggests that activation of kappa opiate receptors may lower mood. However, kappa agonists may also induce psychotomimetic symptoms. We tested the effects of the kappa agonist pentazocine in patients in the manic phase of bipolar disorder to determine if pentazocine might reduce symptoms of mania without worsening psychosis. In an open-label, add-on, single-day acute-dose study, ten in-patients with bipolar disorder, type 1, hospitalized for mania received two 50 mg doses of pentazocine 2 h apart. Symptoms of mania were reduced 1 h after each dose, 44% after the first dose and 41% 1 h after the second dose (F=3.69, p=0.01). No adverse effects, including psychotomimetic effects were observed or reported. Sedation was minimal. Further study of pentazocine and other kappa agonists in mania seems warranted.

A gastrin-releasing peptide receptor antagonist blocks d-amphetamine-induced hyperlocomotion and increases hippocampal NGF and BDNF levels in rats

The gastrin-releasing peptide receptor (GRPR) has emerged as a novel molecular target in neurological and psychiatric disorders, and previous animal studies suggest that GRPR antagonists might display cognitive-enhancing and antipsychotic properties. Hyperlocomotion produced by administration of d-amphetamine ( d-AMPH) to rats has been put forward as a model of the manic phase of bipolar disorder (BD). In the present study, we examined the effects of a single systemic administration of the GRPR antagonist [D-Tpi 6, Leu 13 psi(CH 2NH)-Leu 14] bombesin (6–14) (RC-3095) on hyperlocomotion induced by a single systemic injection of d-AMPH in male rats. We also evaluated the levels of brain-derived neurotrophic factor (BDNF) and nerve growth factor (NGF) in the hippocampus of rats treated with d-AMPH and RC-3095. Administration of RC-3095 at any of the doses used blocked d-AMPH-induced hyperlocomotion. Specific doses of RC-3095 increased the levels of NGF and BDNF in the dorsal hippocampus. Administration of d-AMPH did not affect NGF or BDNF levels by itself, but blocked the RC-3095 effects. The results suggest that GRPR antagonists might display anti-manic activity.

Chronic lamotrigine does not alter the turnover of arachidonic acid within brain phospholipids of the unanesthetized rat: implications for the treatment of bipolar disorder

Drugs that are effective in treating the manic phase of bipolar disorder (lithium, carbamazepine, and valproate) upon chronic administration to rats decrease the turnover of arachidonic acid in their brain phospholipids. Lamotrigine may not be effective in the manic phase, but is effective in delaying the depressive phase and for treating rapid cycling bipolar disorder. Thus, lamotrigine provides a pharmacological tool to differentiate if downregulation of arachidonic acid turnover is specific to drugs effective in the manic phase of bipolar disorder. To test this hypothesis, rats were administered lamotrigine (10 mg kg(-1) day(-1)) or vehicle intragastrically once daily for 42 days. In the unanesthetized rat, [1-(14)C]arachidonic acid was infused intravenously and arterial blood plasma was sampled until the animal was killed at 5 min, and its microwaved brain was subjected to chemical and radiotracer analysis. Using equations from our fatty acid model, we found that chronic lamotrigine compared with vehicle did not alter the net incorporation rate of plasma arachidonic acid into brain phospholipids, nor did it alter the turnover of arachidonic acid within brain phospholipids. Chronic lamotrigine, which is effective in the depressive phase or rapid cycling bipolar disorder does not alter brain arachidonic acid turnover in the unanesthetized rat. These results are consistent with the hypothesis that drugs effective in treating the manic phase of bipolar disorder decrease brain arachidonic acid turnover.

Transgenic Mice Overexpressing Glycogen Synthase Kinase 3β: A Putative Model of Hyperactivity and Mania

Lithium is used as treatment for bipolar disorder with particular efficacy in the treatment of mania. Lithium inhibits glycogen synthase kinase 3beta (GSK-3beta) directly or indirectly via stimulation of the kinase Akt-1. We therefore investigated the possibility that transgenic mice overexpressing GSK-3beta could be of relevance to model bipolar disorder. Transgenic mice showed hypophagia, an increased general locomotor activity, and decreased habituation as assessed in an open field, an increased acoustic startle response, and again decreased habituation. The forced swim test revealed a reduced immobility in transgenic mice, but this is probably related to the hyperactivity of the animals. There were no differences in baseline and stress-induced increases of plasma adrenocorticotrophic hormone and corticosterone levels. Molecular analysis suggests compensatory mechanisms in the striatum of these transgenic mice for the overload of active GSK-3beta by dimming the endogenous GSK-3beta signaling pathway via upregulation of Akt-1 expression. Brain-derived neurotrophic factor protein levels were increased in the hippocampus of the transgenic mice. This suggests some kind of compensatory mechanism to the observed reduction in brain weight, which has been related previously to a reduced size of the somatodendritic compartment. Together, in mice overexpressing GSK-3beta, specific intracellular signaling pathways are affected, which is accompanied by altered plasticity processes and increased activity and reactivity, whereas habituation processes seem to be decreased. The behavioral observations led to the suggestion that the model at hand recapitulates hyperactivity as observed in the manic phase of bipolar disorder.

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The results of a major study have confirmed the potential of quetiapine (Seroquel) as a monotherapy for acute bipolar depression. Quetapine is an atypical antipsychotic and it is already established as an effective treatment for schizophrenia and in the manic phases of bipolar disorder, but it is not approved for the treatment of bipolar depression.

Can Psychiatrists Recognize Mental Illness in Paintings?

Back to table of contents Previous article Next article Images in PsychiatryFull AccessCan Psychiatrists Recognize Mental Illness in Paintings?ANJALI RAOMATCHERI S. KESHAVAN M.D.ANJALI RAOSearch for more papers by this authorMATCHERI S. KESHAVAN M.D.Search for more papers by this authorPublished Online:1 Apr 2006AboutSectionsPDF/EPUB ToolsAdd to favoritesDownload CitationsTrack Citations ShareShare onFacebookTwitterLinked InEmail It is widely believed that mental illness is reflected in paintings of mentally ill artists (1) . Examples include Van Gogh’s “blue” period (depression) and “pink” period (manic phase of bipolar disorder) (2) and Louis Wain’s cat paintings (progressive deterioration to complete incoherence, paralleling schizophrenia) (3) . However, when we asked 12 psychiatrists to evaluate randomly selected paintings created by individuals with 1) schizophrenia, 2) bipolar disorder, and 3) no psychiatric illness (N=10 for each), they were unable to differentiate paintings by artists with and without mental illness. We then randomly selected paintings of four artists with known bipolar disorder (Paul Gauguin, Edward Münch, Vincent van Gogh, Mark Rothko). We asked 12 psychiatrists and 12 laypersons matched for education to determine the period of creation (before or after onset of mental illness), first for individual paintings grouped by artist and then for sets of paintings for each artist. Psychiatrists could reliably identify paintings created before and after onset of mental illness both individually (χ 2 =31.42, df=1, p<0.001) and in sets (χ 2 =17.34, df=1, p<0.01). In contrast, laypersons were able to recognize mental illness only from sets of paintings (χ 2 =4.32, df=1, p<0.05), not from individual paintings. The potential clinical significance of psychiatrists’ ability to recognize mental illness in paintings before and after an episode of psychiatric illness needs further study in individuals other than famous artists.Address correspondence and reprint requests to Dr. Keshavan, UPMC Health System-Western Psychiatric Institute and Clinic, Room 441, 3811 O’Hara St., Pittsburgh, PA 15213; [email protected] (e-mail). Images reproduced by permission of ARS, © 2005 The Munch Museum/The Munch-Ellingsen Group/Artists Rights Society (ARS), New York.

Risperidone for bipolar disorders

Atypical antipsychotic medications are a relatively new, increasingly prominent component of the treatment armamentarium for bipolar disorder – a development that provides more options for potentially improved outcomes for patients and families affected by bipolar disorder. The US Food and Drug Administration-approved bipolar indications for risperidone include monotherapy for the short-term treatment of acute manic or mixed episodes associated with bipolar I disorder and combination therapy with lithium or valproate for the short-term treatment of acute manic or mixed episodes associated with bipolar I disorder. Risperidone is also approved in over 30 countries worldwide for bipolar mania either as monotherapy, adjunct therapy, or both monotherapy and adjunct therapy. A number of controlled and open-label treatment trials have shown risperidone’s efficacy and tolerability in the manic phase of bipolar disorder. Risperidone has also been reported to be useful in the longer-term treatment of bipolar disorder. This drug profile of risperidone for bipolar disorder will address the chemistry, pharmacodynamics, pharmacokinetics and metabolism of risperidone, clinical trials in bipolar disorder, postmarketing surveillance, safety, tolerability and regulatory issues. Finally, a discussion of potential future directions, a summary of key issues and information resources are provided.

Divalproex in the treatment of bipolar depression: a placebo-controlled study

Background The treatment of bipolar disorder in the depressed phase is complicated by a tendency for conventional antidepressant drugs to worsen the course of the illness by precipitating a manic episode or increasing cycle frequency. Thus, the potential antidepressant efficacy of mood stabilizers, such as divalproex, which is an effective treatment for the manic phase of bipolar disorder, is of considerable interest. Methods The clinical efficacy of divalproex (valproate, Depakote®) was tested in an 8-week, double-blind, placebo-controlled, randomized clinical trial in 25 outpatients with bipolar I depression. The primary outcome measure was the 17-item Hamilton Rating Scale for Depression, and secondary measures included the Hamilton Rating Scale for Anxiety, the Clinician Administered Rating Scale for Mania, and the Clinical Global Impression scale. Results Using repeated measures ANOVA with last observation carried forward, divalproex was more effective than placebo in improving symptoms of depression ( p=0.0002) and symptoms of anxiety ( p=0.0001) than placebo. Limitations The sample size was small, and most patients were male. Conclusions These pilot results indicate that divalproex is effective in reducing the symptoms of depression and anxiety in bipolar I, depressed phase. These positive results support the need to perform a larger, multisite study of divalproex treatment for bipolar depression.

Bipolar depression: the role of atypical antipsychotics

Acute manic episodes in bipolar disorder require rapid and effective relief. Bipolar depression is a major component of the bipolar disorder spectrum. Existing treatment options for bipolar depression include lithium, lamotrigine and conventional antidepressants. However, lithium is more effective in treating mania or hypomania than depression, both acutely and prophylactically, lamotrigine has only been demonstrated to be effective in one adequately powered study in acute bipolar I depression, and conventional antidepressants have been associated with emergent mania and cycle acceleration. Symptomatic outpatients can expect to spend, on average, 33% of their time in the depressive phase compared with 11% in the manic phase. Consequently, there is a need for additional agents to effectively treat bipolar depression. The atypical agents olanzapine, risperidone and quetiapine have demonstrated efficacy against the manic phase of bipolar disorder and appear also to have potential in the depressive phase. Olanzapine monotherapy significantly improved depressive symptoms compared with placebo in patients with bipolar disorder in an 8-week randomized, controlled clinical study, but the magnitude of the clinical effect was small. The observed improvement in depressive symptoms became moderately large when olanzapine was combined with the antidepressant fluoxetine. Quetiapine monotherapy also resulted in significant improvements compared with placebo in patients with either bipolar I or bipolar II disorder in another 8-week randomized, controlled clinical study, but the effect size was large. A 6-month open-label study of risperidone added to ongoing therapy demonstrated improvements in depressive symptoms in patients with bipolar and schizoaffective disorders experiencing a manic, hypomanic, mixed or depressive episode. The receptor-binding profile of these agents supports a role in the treatment of depressive symptoms and clinical data are beginning to emerge of their efficacy in both the acute and maintenance setting.

Risperidone in the treatment of mania: efficacy and safety results from a large, multicentre, open study in Spain

Background: A number of open studies and preliminary results of unpublished double-blind trials have suggested that the novel antipsychotic risperidone may be effective and well tolerated in the treatment of acute mania in bipolar disorder. Methods: A total of 174 patients entered this large, open, multicentre trial. Inclusion criteria were: current manic, hypomanic or mixed episode (DSM-IV), and a Young Mania Rating Scale (YMRS) score of >7. Assessments included the YMRS, Positive and Negative Syndrome Scale (PANSS), Hamilton Rating Scale for Depression (HAM-D), Clinical Global Impression (CGI), and Udvalg for Kliniske Undersøgelser (UKU) subscale for neurological side effects. Results: There were significant reductions ( P<0.0001) on the YMRS, PANSS and HAM-D scores and a significant improvement ( P<0.0001) in CGI ratings at the endpoint. There were no statistically significant increments in the severity of extrapyramidal symptoms according to the UKU. Risperidone was generally well tolerated. The mean dose of risperidone at the endpoint was 4.9±2.9 mg/day. Conclusions and clinical implications: This open study provides further evidence that risperidone is safe and effective in combination with mood stabilisers in the manic phase of bipolar disorder. Limitations: The open design and the use of concomitant medications make unclear to what extent the positive results were entirely related to risperidone.

Droperidol for acute psychosis.

People with acute psychotic illnesses, especially when associated with agitated or violent behaviour, may require urgent pharmacological tranquillisation or sedation. Droperidol, a butyrophenone neuroleptic, is used for this purpose in several countries. To estimate the effects of droperidol when compared to other treatments for controlling disturbed behaviour and reducing psychotic symptoms for people with suspected acute psychotic illnesses. The Cochrane Controlled Trials Register (Issue 2, 2000), The Cochrane Schizophrenia Group's Register (May 2000), EMBASE (1980-2000), MEDLINE (1966-2000), PASCAL (1973-2000) and PsycLIT (1970-2000) were methodically searched. Twenty-one other databases were also searched as part of a broader project and this composite database was searched for this review. This was supplemented by hand searching reference lists, contacting industry and relevant authors. Randomised clinical trials comparing droperidol to any treatment, for people with suspected acute psychotic illnesses, such as schizophrenia, schizoaffective disorder, mixed affective disorders, manic phase of bipolar disorder or brief psychotic episode. Studies were reliably selected, quality assessed and data extracted. Data were excluded where more than 50% of participants were lost to follow up. For binary outcomes, standard estimations of risk ratio (RR) and their 95% confidence intervals (CI) were calculated. Where possible, weighted number needed to treat or harm statistics (NNT, NNH), and their 95% confidence intervals (CI), were also calculated. Only two clearly relevant randomised trials with usable data were identified. One additional study was included but focused on outcomes at 30 days rather than a few hours. One small (n=41) randomised trial compared droperidol (10mg IV) with placebo IV and found that people allocated to droperidol were significantly less likely to need additional haloperidol injections in the first few minutes (n=41, RR 0.37 CI 0.2 to 0.7, NNT 2 CI 1 to 10) than those given placebo. By 90 minutes this difference was still evident but not statistically significant (RR 0.46 CI 0.2 to 1.2). When 5mg IM droperidol was compared to 5mg IM haloperidol people given droperidol were again less likely to need additional injections by 30 minutes, than those given haloperidol, but this result did not quite reach conventional levels of statistical significance (n=27, RR 0.45 CI 0.2 to 1.01). One person out of 16 given haloperidol experienced a mild dystonic reaction, and none of the 11 people allocated to droperidol were reported to have experienced adverse effects. This is an important and surprisingly under-researched area. Use of droperidol for the emergency situation is currently justified on experience rather than evidence from well conducted and reported randomised trials.

Clotiapine for acute psychotic illnesses.

Acute psychotic illness, especially when associated with agitated or violent behaviour, requires urgent pharmacological tranquillisation or sedation. Clotiapine, a dibenzothiazepine neuroleptic, is being used for this purpose in several countries. To estimate the effects of clotiapine when compared to other 'standard' or 'non-standard' treatments of acute psychotic illness in controlling disturbed behaviour and reducing psychotic symptoms. The Cochrane Controlled Trials Register (Issue 2, 2000), The Cochrane Schizophrenia Group's Register (May 2000), EMBASE (1980-2000), MEDLINE (1966-2000), PASCAL (1973-2000) and PsycLIT (1970-2000) were methodically searched. This was supplemented by hand searching reference lists, contacting industry and relevant authors. Randomised clinical trials comparing clotiapine to any treatment, for people with acute psychotic illnesses such as in schizophrenia, schizoaffective disorder, mixed affective disorders, manic phase of bipolar disorder, brief psychotic episode or organic psychosis following substance abuse. Studies were reliably selected, quality assessed and data extracted. Data were excluded where more than 50% of participants in any group were lost to follow up. For binary outcomes a standard estimation of the risk ratio (RR) and its 95% confidence interval (CI) was calculated. Where possible, the weighted number needed to treat statistic (NNT), and its 95% confidence interval (CI), was also calculated. If heterogeneity was found, a random effects model was used. For continuous outcomes, endpoint data were preferred to change data. Non-skewed data from valid scales were summated using a weighted mean difference (WMD). Again, if heterogeneity was found a random effects model was used. A Mantel-Haenszel chi-square test was used to investigate the possibility of heterogeneity. Five trials were included. None compared clotiapine with placebo, but control drugs were either antipsychotics (chlorpromazine, perphenazine, trifluoperazine and zuclopenthixol acetate) or benzodiazepines (lorazepam). Versus antipsychotics: results for global clinical outcome were heterogeneous (p=0.09) but did not suggest clotiapine to be superior, or inferior, to chlorpromazine, perphenazine, or trifluoperazine (total randomised = 83). Use of clotiapine did change the proportion of people ready for hospital discharge by the end of the study in one small trial (n=49, RR 1.04 95%CI 0.96 to 2.12). Overall, attrition rates were low. No significant difference was found for those allocated to clotiapine compared with people randomised to other antipsychotics (n=121, RR 2.26 95%CI 0.40 to 13). Weak data suggests that clotiapine may result in less need for antiparkinsonian treatment compared with zuclopenthixol acetate (n=38, RR 0.43 95%CI 0.02 to 0.98). Versus lorazepam: when used to control aggressive/violent outbursts for people already treated with haloperidol, clotiapine did not significantly improve mental state compared to lorazepam (WMD -3.36 95%CI -8.09 to 1.37). Much data could not be pooled due to skew or inadequate presentation of results. Economic outcomes and satisfaction with care were not addressed. We found no significant evidence to support the use of clotiapine rather than other 'standard' or 'non-standard' treatments for the management of acute psychotic illness. The trials included in this review all present important methodological flaws. We do not wish to discourage clinicians from using clotiapine in the psychiatric emergency, we would just like to point out the fact that good quality controlled trials are needed on this subject.

The efficacy of ECT in mixed affective states.

ECT is efficacious in the treatment of both the depressed and manic phases of bipolar disorder. While ECT is believed to be equally efficacious in the treatment of mixed affective states, to our knowledge there are no empirical studies on this issue. A chart review study was conducted to compare treatment response and clinical course in three groups of patients who received ECT in a general hospital service: bipolar depressed (n = 38), bipolar manic (n = 5), and bipolar mixed (n = 10), diagnosed by DSM-IV criteria. All three groups showed robust response rates, but the number of days of hospitalization was significantly longer in the mixed group (mean 30, SD 19.0 days) compared with the depressed group (mean 19.0, SD 10.9 days, t = 2.4, p < 0.03). There was a trend for the number of ECT treatments to be greater in the mixed compared with the depressed group. These findings indicate that patients with mixed affective states do respond well to a course of ECT, but the longer hospital stays and greater number of ECT treatments suggest that they may be more difficult to treat with ECT than patients with pure bipolar depression or bipolar mania.

Lack of linkage between the corticotropin-releasing hormone (CRH) gene and bipolar affective disorder.

Corticotropin-releasing hormone (CRH) plays a key role in the regulation of the stress response. Abnormalities in CRH secretion have been documented in both the depression and manic phases of bipolar disorder (BPD). In the present study, we investigated genetic linkage between the CRH gene and BPD in 22 pedigrees. A highly informative, short tandem repeat (STR) polymorphism adjacent to the CRH gene on human chromosomal region 8q13 was used to examine linkage. Affected sibling pair (ASP) and the likelihood-based disequilibrium tests revealed nonsignificant values. We conclude that the CRH gene is not linked to BPD; if genes involved in the regulation of stress response are indeed linked to BPD, the search should be directed towards those that regulate CRH secretion or its effects on target tissues.

Strategies for managing depression complicated by bipolar disorder, suicidal ideation, or psychotic features.

Major depression, a common clinical problem that, if recognized early and treated vigorously, is often highly responsive to antidepressants and can be complicated by such features as mania, suicidal thoughts and actions, and psychosis. Suicide is one of the most serious complications of major depression. An online search of the medical literature was used to select English-language articles addressing depression using, but not limited to, the following specific terms: "primary care," "depressive disorders," "bipolar disorder," "suicide," "psychosis," and "antidepressants." Treatment of the manic phases of bipolar disorder includes lithium or anticonvulsants. Breakthrough depression can be particularly resistant to treatment in bipolar patients, and the tricyclic antidepressants can cause patients to cycle more rapidly into the manic phase. The selective serotonin reuptake inhibitors (SSRIs) and bupropion are less likely to cause rapid cycling in bipolar disorder. Depressed patients with suicidal tendencies should be closely monitored and given full doses of antidepressant medications. The SSRIs lessen suicidal tendencies and, importantly, are markedly safer than the tricyclic antidepressants when taken in an overdose. Depressed patients can also become psychotic, exhibiting mood-congruent delusions. Combination therapy with antidepressant and antipsychotic medications is often necessary. Some physicians prefer to hospitalize patients with psychotic depression. Depression can be a complex and multifaceted disorder that requires careful diagnosis and treatment plans.

Treatment of Depression in Bipolar Disorder

The objective of the study was to review the clinical literature on the acute, somatic treatment of the depressed phase of bipolar disorder. We reviewed all available published studies of "standard" somatic treatments (lithium, antidepressant and anticonvulsant agents, and electroconvulsive therapy [ECT]) reporting three or more depressed bipolar patients who were not psychotic, rapid cycling, or previously treatment refractory. We also reviewed all studies of "nonstandard" pharmacologic treatments involving even a single case of a depressed bipolar patient. Data sources included the MEDLINE database and relevant references from articles obtained in this search and in major reviews. Five of seven studies comparing ECT with antidepressant agents find ECT more efficacious. Eight of nine controlled comparisons find lithium superior to placebo in depressed bipolar patients. Three controlled comparisons of lithium to tricyclic antidepressants suggest that lithium is equivalent to tricyclic drugs in such patients. Three double-blind, controlled studies indicate that carbamazepine is more effective than placebo. Limited data on other antidepressant classes suggest that monoamine oxidase inhibitors, bupropion, and serotonergic agents may offer some advantages over tricyclic antidepressants in this population. Some "nonstandard" treatments also show some potential in bipolar patients. The possibility of switching into a manic episode is an important consideration with many of the agents studied, although little remains known about spontaneous versus treatment-associated mood shifts. In contrast to the extensive literature on the acute treatment of the manic phase of bipolar disorder and on the prophylaxis of manic and depressive episodes, there are few studies of treatment of the depressed phase of bipolar disorder, and their results generally are limited or inconclusive. Lithium generated a revolution in psychiatric treatment, but the treatment of the depressed phase of bipolar disorder remains a relatively neglected corner of the field. Several study designs may help to augment knowledge in the treatment of bipolar depression.