Bipolar Disorder and Suicide -- Neurotransmitter.net

(Updated 1/12/04)

Muller-Oerlinghausen B, Berghofer A, Bauer M.
Bipolar disorder.
Lancet 2002 Jan 19;359(9302):241-7
"Bipolar, or manic-depressive, disorder is a frequent, severe, mostly recurrent mood disorder associated with great morbidity. The lifetime prevalence of bipolar disorder is 1.3 to 1.6%. The mortality rate of the disease is two to three times higher than that of the general population. About 10-20% of individuals with bipolar disorder take their own life, and nearly one third of patients admit to at least one suicide attempt. The clinical manifestations of the disease are exceptionally diverse. They range from mild hypomania or mild depression to severe forms of mania or depression accompanied by profound psychosis. Bipolar disorder is equally prevalent across sexes, with the exception of rapid cycling, a severe and difficult to treat variant of the disorder, which arises mostly in women. Because of the high risk of recurrence and suicide, long-term prophylactic pharmacological treatment is indicated." [Abstract]

Rihmer Z, Kiss K.
Bipolar disorders and suicidal behaviour.
Bipolar Disord. 2002;4 Suppl 1:21-5.
"Major depressive disorder is the leading cause of suicide, particularly in the absence of adequate treatment. The aim of this paper is to analyse the relationship between different forms of major mood disorders and suicidal behaviour. Population-based epidemiological surveys as well as clinical studies on the clinically explorable suicide risk factors in bipolar and unipolar depressive disorders are reviewed. The present literature shows that patients with bipolar disorders are at higher risk of attempted and completed suicide than that of patients with unipolar major depression. Contrasting only bipolar I and bipolar II patients, current findings indicate that the rate of prior suicide attempt is higher in bipolar II patients, and bipolar II disorder is overrepresented in depressed suicide victims. Among patients with different clinical manifestations of major mood disorders (unipolar major depression. bipolar I and bipolar II disorder), bipolar patients in general, and bipolar II subjects in particular carry the highest risk of suicide." [Abstract]

Rihmer Z, Pestality P.
Bipolar II disorder and suicidal behavior.
Psychiatr Clin North Am 1999 Sep;22(3):667-73, ix-x
"Despite the fact that the nosologic position of bipolar II disorder continues to be debated, several lines of research indicate that it is a distinct nosologic category that should be separated from both bipolar I and unipolar major depression. This review of the authors' and others' work demonstrates that the lifetime risk of suicide attempts is highest in bipolar II and lowest in unipolar patients, whereas risk is intermediate in bipolar I patients. Moreover, two reports show that bipolar II patients are over represented among suicide victims. Clinicians must take great care in not missing this diagnosis, which, when untreated, has ominous prognostic implications." [Abstract]

Oquendo MA, Mann JJ.
Identifying and managing suicide risk in bipolar patients.
J Clin Psychiatry 2001;62 Suppl 25:31-4
"Bipolar patients have been shown to be at high risk for suicidal behavior. Therefore, identifying potentially suicidal patients is necessary in the treatment of bipolar patients. A stress-diathesis model for suicidal behavior has been proposed to assist clinicians in determining which patients are at risk. In the model, suicidal behavior is the result of the interaction between an individual's threshold for suicidal acts and the stressors that can lead to suicidal behavior. Suicide risk factors can then be categorized as either diathesis-related or stress-related. In a study applying the model of suicidal behavior to bipolar disorder, bipolar patients who attempted suicide had higher levels of suicidal ideation, lifetime aggression, and substance abuse than the comparison group of nonattempters. Attempters had twice the number of major depressive episodes. Once high-risk patients are identified, their suicide risk can be managed through treatments such as prophylactic lithium treatment and other pharmacologic approaches." [Abstract]

Dalton EJ, Cate-Carter TD, Mundo E, Parikh SV, Kennedy JL.
Suicide risk in bipolar patients: the role of co-morbid substance use disorders.
Bipolar Disord. 2003 Feb;5(1):58-61.
"OBJECTIVE: Bipolar disorder is associated with a high frequency of both completed suicides and suicide attempts. The primary aim of this study was to identify clinical predictors of suicide attempts in subjects with bipolar disorder. METHODS: We studied 336 subjects with a diagnosis of bipolar I, bipolar II, or schizoaffective disorder (bipolar type). The Structured Clinical Interview for DSM-IV (SCID-I) was administered and subsequently two expert psychiatrists established a diagnosis. Predictors of suicide attempts were examined in attempters and non-attempters. RESULTS: The lifetime rate of suicide attempts for the entire sample was 25.6%. A lifetime co-morbid substance use disorder was a significant predictor of suicide attempts: bipolar subjects with co-morbid substance use disorders (SUD) had a 39.5% lifetime rate of attempted suicide, while those without had a 23.8% rate (odds ratio = 2.09, 95% CI = 1.03-4.21, chi2 = 4.33, df = 1, p = 0.037). CONCLUSIONS: Lifetime co-morbid SUD were associated with a higher rate of suicide attempts in patients with bipolar disorder. This relationship may have a genetic origin and/or be explained by severity of illness and trait impulsivity." [Abstract]

Daskalopoulou EG, Dikeos DG, Papadimitriou GN, Souery D, Blairy S, Massat I, Mendlewicz J, Stefanis CN.
Self-esteem, social adjustment and suicidality in affective disorders.
Eur Psychiatry. 2002 Sep;17(5):265-71.
"Self-esteem (SE) and social adjustment (SA) are often impaired during the course of affective disorders; this impairment is associated with suicidal behaviour. The aim of the present study was to investigate SE and SA in unipolar or bipolar patients in relation to demographic and clinical characteristics, especially the presence of suicidality (ideation and/or attempt). Forty-four patients, 28 bipolar and 16 unipolar, in remission for at least 3 months, and 50 healthy individuals were examined through a structured clinical interview. SE and SA were assessed by the Rosenberg self-esteem scale and the social adjustment scale, respectively. The results have shown that bipolar patients did not differ from controls in terms of SE, while unipolar patients had lower SE than bipolars and controls. No significant differences in the mean SA scores were found between the three groups. Suicidality during depression was associated only in bipolar patients with lower SE at remission; similar but not as pronounced was the association of suicidality with SA. It is concluded that low SE lasting into remission seems to be related to the expression of suicidality during depressive episodes of bipolar patients, while no similar pattern is evident in unipolar patients." [Abstract]

Simpson SG, Jamison KR.
The risk of suicide in patients with bipolar disorders.
J Clin Psychiatry 1999;60 Suppl 2:53-6; discussion 75-6, 113-6
"Patients with bipolar disorder have a high risk of committing suicide, but determining the exact risk is complicated. For many years, the lifetime suicide risk in bipolar disorder was accepted as 15%, but recent researchers have suggested that the lifetime suicide risk may be lower. The group of bipolar patients at highest risk of suicide are young men who are in an early phase of the illness, especially those who have made a previous suicide attempt, those abusing alcohol, and those recently discharged from the hospital. The risk is also increased in patients who are in the depressed phase of bipolar illness, who have mixed states, or who have psychotic mania." [Abstract]

Vieta E, Colom F, Gasto C, Nieto E, Benabarre A, Otero A.
[Bipolar II disorder: course and suicidal behavior]
Actas Luso Esp Neurol Psiquiatr Cienc Afines 1997 May-Jun;25(3):147-51
"INTRODUCTION: Bipolar II disorder seems to be more than a mild form of classic manic-depressive illness. Differences with bipolar I concern genetic, biological, clinical and pharmacological aspects. Nevertheless, studies on suicidal behavior in both groups have resulted in inconsistent results PATIENTS AND METHOD: Twenty-two patients fulfilling Research Diagnostic Criteria for the diagnosis of bipolar II disorder and 38 bipolar I were evaluated with the Schedule for Affective Disorders and Schizophrenia by two independent interviewers, and compared. RESULTS: Bipolar II patients had significantly more previous episodes (p = 0.001), including both depressive (p = 0.003) and hypomanic switches (p = 0.006), but had been hospitalized (p = 0.001) and presented psychotic symptoms (p < 0.001) less frequently. CONCLUSIONS: There were no significant differences between both groups regarding suicidal behavior variables. These results suggest that bipolar II disorder is less severe than bipolar I regarding symptoms intensity, but more severe with respect to episodes frequency, and that suicide attempts rates are not useful to discriminate between both groups." [Abstract]

Leverich GS, Altshuler LL, Frye MA, Suppes T, Keck PE Jr, McElroy SL, Denicoff KD, Obrocea G, Nolen WA, Kupka R, Walden J, Grunze H, Perez S, Luckenbaugh DA, Post RM.
Factors associated with suicide attempts in 648 patients with bipolar disorder in the Stanley Foundation Bipolar Network.
J Clin Psychiatry. 2003 May;64(5):506-15.
"BACKGROUND: Clinical factors related to suicide and suicide attempts have been studied much more extensively in unipolar depression compared with bipolar disorder. We investigated demographic and course-of-illness variables to better understand the incidence and potential clinical correlates of serious suicide attempts in 648 outpatients with bipolar disorder. METHOD: Patients with bipolar I or II disorder (DSM-IV criteria) diagnosed with structured interviews were evaluated using self-rated and clinician-rated questionnaires to assess incidence and correlates of serious suicide attempts prior to study entry. Clinician prospective ratings of illness severity were compared for patients with and without a history of suicide attempt. RESULTS: The 34% of patients with a history of suicide attempts, compared with those without such a history, had a greater positive family history of drug abuse and suicide (or attempts); a greater personal history of early traumatic stressors and more stressors both at illness onset and for the most recent episode; more hospitalizations for depression; a course of increasing severity of mania; more Axis I, II, and III comorbidities; and more time ill on prospective follow-up. In a hierarchical logistic regression, a history of sexual abuse, lack of confidant prior to illness onset, more prior hospitalizations for depression, suicidal thoughts when depressed, and cluster B personality disorder remained significantly associated with a serious suicide attempt. CONCLUSION: Our retrospective findings, supplemented by prospective follow-up, indicate that a history of suicide attempts is associated with a more difficult course of bipolar disorder and the occurrence of more psychosocial stressors at many different time domains. Greater attention to recognizing those at highest risk for suicide attempts and therapeutic efforts aimed at some of the correlates identified here could have an impact on bipolar illness-related morbidity and mortality." [Abstract]

Oquendo MA, Waternaux C, Brodsky B, Parsons B, Haas GL, Malone KM, Mann JJ.
Suicidal behavior in bipolar mood disorder: clinical characteristics of attempters and nonattempters.
J Affect Disord 2000 Aug;59(2):107-17
"OBJECTIVE: Bipolar Disorder is associated with a higher frequency of attempted suicide than most other psychiatric disorders. The reasons are unknown. This study compared bipolar subjects with a history of a suicide attempt to those without such a history, assessing suicidal behavior qualitatively and quantitatively, and examining possible demographic, psychopathologic and familial risk factors. METHODS: Patients (ages 18 to 75) with a DSM III-R Bipolar Disorder (n = 44) diagnosis determined by a structured interview for Axis I disorders were enrolled. Acute psychopathology, hopelessness, protective factors, and traits of aggression and impulsivity were measured. The number, method and degree of medical damage was assessed for suicide attempts, life-time. RESULTS: Bipolar suicide attempters had more life-time episodes of major depression, and twice as many were in a current depressive or mixed episode, compared to bipolar nonattempters. Attempters reported more suicidal ideation immediately prior to admission, and fewer reasons for living even when the most recent suicide attempt preceded the index hospitalization by more than six months. Attempters had more lifetime aggression and were more likely to be male. However, attempters did not differ from nonattempters on lifetime impulsivity. LIMITATIONS: The generalizability of the results is limited because this is a study of inpatients with a history of suicide attempts. Patients with Bipolar I and NOS Disorders were pooled and a larger sample is needed to look at differences. We could not assess psychopathology immediately prior to the suicide attempt because, only half of the suicide attempters had made attempts in the six months prior to admission. Patients with current comorbid substance abuse were excluded. No suicide completers were studied. CONCLUSIONS: Bipolar subjects with a history of suicide attempt experience more episodes of depression, and react to them by having severe suicidal ideation. Their diathesis for acting on feelings of anger or suicidal ideation is suggested by a higher level of lifetime aggression and a pattern of repeated suicide attempts." [Abstract]
Michaelis BH, Goldberg JF, Singer TM, Garno JL, Ernst CL, Davis GP.
Characteristics of first suicide attempts in single versus multiple suicide attempters with bipolar disorder.
Compr Psychiatry. 2003 Jan-Feb;44(1):15-20.
"Although suicidality remains highly prevalent among patients with bipolar disorder, little research exists examining the characteristics of successive attempts among individuals who make and survive a first suicide attempt. We compared bipolar subjects with a history of one suicide attempt to those with multiple attempts and assessed demographic characteristics, family histories, psychopathology, and clinical dimensions of suicidal behavior. Fifty-two DSM-IV bipolar patients (age 21 to 74 years) with a history of at least one suicide attempt were consecutively evaluated in the Bipolar Disorders Research Clinic of the New York Presbyterian Hospital. Circumstances surrounding each lifetime suicide attempt were assessed by direct interviews, questionnaires, and chart reviews along with family psychiatric histories, substance abuse histories, current psychopathology, and features of impulsivity and aggression. Multiple suicide attempts occurred in approximately two thirds of the study group. Single attempters were significantly more likely than multiple attempters to show high seriousness of intent at their first attempt (OR = 0.65, 95% CI = 0.43 to 0.99), and tended to be less likely than multiple attempters to exhibit mixed states at their first attempt (OR = 0.54, 95% CI = 0.28 to 1.01). Seriousness of intent was consistent across the first and second attempts (r =.48, P <.01) and second and third attempts (r =.74, P <.05). Single and multiple attempters differed in no other clinical or demographic characteristics studied. We conclude that multiple suicide attempts are common among bipolar patients. Those who survive an initial suicide attempt involving high seriousness of intent appear less likely than those with low intent to make subsequent attempts. Consequently, single attempters may represent a group more closely resembling those who complete suicide on a first attempt, in terms of the risk for death associated with their first attempt. However, multiple suicide attempts among bipolar patients are not necessarily associated with a higher risk for lethality in first suicide attempt survivors." [Abstract]

Shyovitz M.
A family member's legal experience with an insurer's refusal to recertify inpatient mental health treatment.
J Clin Psychiatry 2001;62 Suppl 25:44-50
"My son Nathaniel has bipolar disorder and was hospitalized for 6 months, during which time our insurance company was prepared to refuse certification more than once despite a policy that included 365 days of inpatient mental health treatment. A break in coverage by the insurance company would have meant that Nathaniel, still suicidal, would not receive the life-saving care he needed. Fortunately, I am a lawyer, which enabled me to act as a legal advocate for my son when our insurer threatened not to recertify. Because my son's experience with the insurance company is not unusual--many patients with mental illness struggle with insurance companies who refuse to certify treatment--I believe that the family or support people of seriously ill psychiatric patients should be prepared to act in circumstances similar to mine. Psychiatric inpatient units should, as a matter of course, provide information on legal remedies that can be obtained before irreparable harm occurs." [Abstract]
Gray SM, Otto MW.
Psychosocial approaches to suicide prevention: applications to patients with bipolar disorder.
J Clin Psychiatry 2001;62 Suppl 25:56-64
"Hopelessness, dysfunctional attitudes, and poor problem-solving abilities are psychosocial risk factors that have been identified as predictors of suicide. These psychosocial risk factors may help clinicians apply specific therapies and treatments to patients with bipolar disorder at risk for suicide. A search of the literature on suicide prevention revealed 17 randomized, controlled studies, which the authors reviewed to determine the efficacy of strategies aimed at eliminating psychosocial risk factors for suicide. Three strategies emerged as efficacious: (1) applying interventions to elicit emergency care by patients at times of distress; (2) training in problem-solving strategies; and (3) combining comprehensive interventions that include problem solving with intensive rehearsal of cognitive, social, emotional-labeling, and distress-tolerance skills. On the basis of their review of the literature, the authors make recommendations for suicide prevention for patients with bipolar disorder." [Abstract]
Potash JB, Kane HS, Chiu YF, Simpson SG, MacKinnon DF, McInnis MG, McMahon FJ, DePaulo JR Jr.
Attempted suicide and alcoholism in bipolar disorder: clinical and familial relationships.
Am J Psychiatry 2000 Dec;157(12):2048-50
"OBJECTIVE: This study examined the clinical and familial relationships between comorbid alcoholism and attempted suicide in affectively ill relatives of probands with bipolar I disorder. METHOD: In 71 families ascertained for a genetic linkage study, 337 subjects with major affective disorder were assessed by using the Schedule for Affective Disorders and Schizophrenia-Lifetime Version. RESULTS: Subjects with bipolar disorder and alcoholism had a 38.4% lifetime rate of attempted suicide, whereas those without alcoholism had a 21.7% rate. Attempted suicide among subjects with bipolar disorder and alcoholism clustered in a subset of seven families. Families with alcoholic and suicidal probands had a 40.7% rate of attempted suicide in first-degree relatives with bipolar disorder, whereas other families had a 19.0% rate. CONCLUSIONS: Comorbid alcoholism was associated with a higher rate of attempted suicide among family members with bipolar disorder. Attempted suicide and alcoholism clustered in a subset of families. These relationships may have a genetic origin and may be mediated by intoxication, mixed states, and/or temperamental instability." [Abstract]

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Recent Bipolar Disorder & Suicide Research
Sakai T, Oshima A, Nozaki Y, Ida I, Haga C, Akiyama H, Nakazato Y, Mikuni M
Changes in density of calcium-binding-protein-immunoreactive GABAergic neurons in prefrontal cortex in schizophrenia and bipolar disorder.
Neuropathology. 2007 Dec 5;
There is evidence that GABAergic neurotransmission is altered in mental disorders such as schizophrenia (SCZ) and bipolar disorder (BPD). The calcium-binding proteins (CBPs) calbindin (CB), calretinin (CR), and parvalbumin (PV) are used as markers of specific subpopulations of cortical GABAergic interneurons. We examined the postmortem prefrontal cortical region (Brodmann's area 9) of patients with SCZ and BPD, and of age-matched control subjects, excluding suicide cases. The laminar density of neurons immunoreactive (IR) for three CBPs, namely CB, CR, and PV, was quantified. The densities of CB-IR neurons in layer 2 and PV-IR neurons in layer 4 in the SCZ subjects decreased compared with those in the control subjects. When CBP-IR neurons were classified according to their size, a reduction in the density of medium CB-IR neurons in layer 2 in SCZ subjects and an increase in the density of large CR-IR neurons in layer 2 in BPD subjects were observed. These results suggest that alterations in specific GABAergic neurons are present in mental disorders, and that such alterations may reflect the vulnerability toward the disorders. [Abstract]

Tochigi M, Iwamoto K, Bundo M, Sasaki T, Kato N, Kato T
Gene expression profiling of major depression and suicide in the prefrontal cortex of postmortem brains.
Neurosci Res. 2007 Nov 6;
Genome-wide gene expression analysis using DNA microarray has a great advantage to identify the genes or specific molecular cascades involved in mental diseases, including major depression and suicide. In the present study, we conducted DNA microarray analysis of major depression using postmortem prefrontal cortices. The gene expression patterns were compared between the controls and subjects with major depression. As a result, 99 genes were listed as the differentially expressed genes in major depression, of which several genes such as FGFR1, NCAM1, and CAMK2A were of interest. Gene ontology analysis suggested an overrepresentation of genes implicated in the downregulation or inhibition of cell proliferation. The present results may support the hypothesis that major depression is associated with impaired cellular proliferation and plasticity. Comparison between the controls and suicide victims with major depression, bipolar disorder, or schizophrenia was also conducted in the present study. Two genes, CAD and ATP1A3, were differentially expressed in the three comparisons in the same direction. Interestingly, these two genes were also included in the differentially expressed 99 genes in major depression. It may be worth investigating the genes in relation to suicide or major depression. [Abstract]

Young AH, Hammond JM
Lithium in mood disorders: increasing evidence base, declining use?
Br J Psychiatry. 2007 Dec;191474-6.
Use of lithium for the treatment of bipolar disorder may be declining even as knowledge of the efficacy and side-effects of lithium has increased. Recent meta-analyses confirm the benefits of maintenance lithium treatment and show that it reduces suicide and suicidality. Psychiatrists should continue to utilise this efficacious treatment for bipolar disorder. [Abstract]

Munk Laursen T, Munk-Olsen T, Nordentoft M, Bo Mortensen P
A comparison of selected risk factors for unipolar depressive disorder, bipolar affective disorder, schizoaffective disorder, and schizophrenia from a danish population-based cohort.
J Clin Psychiatry. 2007 Nov;68(11):1673-81.
OBJECTIVE: Growing evidence of an etiologic overlap between schizophrenia and bipolar disorder has become increasingly difficult to disregard. In this study, we examined paternal age, urbanicity of place of birth, being born "small for gestational age," and parental loss as risk factors for primarily schizophrenia and bipolar disorder, but also unipolar depressive disorder and schizo-affective disorder. Furthermore, we examined the incidence of the disorders in a population-based cohort and evaluated our results in the context of the Kraepelinian dichotomization. METHOD: We established a register-based cohort study of more than 2 million persons born in Denmark between January 1, 1955, and July 1, 1987. Overall follow-up began on January 1, 1973 and ended on June 30, 2005. Relative risks for schizophrenia, bipolar disorder, unipolar depressive disorder, and schizoaffective disorder (ICD-8 or ICD-10) were estimated by survival analysis, using Poisson regression. RESULTS: Differences were found in age-specific incidences. Loss of a parent (especially by suicide) was a risk factor for all 4 disorders. High paternal age and urbanization at birth were risk factors for schizophrenia. Children born pre-term had an excess risk of all disorders except schizophrenia if they were born "small for gestational age." CONCLUSIONS: An overlap in the risk factors examined in this study was found, and the differences between the phenotypes were quantitative rather than qualitative, which suggests a genetic and environmental overlap between the disorders. However, large gender differences and differences in the age-specific incidences in the 4 disorders were present, favoring the Kraepelinian dichotomization. [Abstract]

Fountoulakis KN, Grunze H, Panagiotidis P, Kaprinis G
Treatment of bipolar depression: An update.
J Affect Disord. 2007 Nov 23;
This article attempts to summarize the current status of our knowledge and practice in the acute treatment and prophylaxis of bipolar depression. For prophylactic treatment, our knowledge about lithium firmly supports its usefulness against bipolar depression and its specific effectiveness for suicidal prevention. Valproic acid and carbamazepine could be effective, too, while lamotrigine which seems to be preferably effective against depression but not mania. The FDA has approved the olanzapine-fluoxetine combination and quetiapine monotherapy for the treatment of acute bipolar depression. The usefulness of antidepressants in bipolar depression is controversial both for acute and prophylactic treatment; guidelines suggest their cautious use and always in combination with an antimanic and mood stabilizer agent, because in some patients they may induce switching to mania or hypomania, mixed episodes and rapid cycling. Data on psychosocial intervention are restricted to the maintenance phase. Electroconvulsive therapy and transcranial magnetic stimulation are additional options for refractory patients. Bipolar depression seems to be a more difficult condition to treat than mania. Most patients need complex combination treatment although the published evidence on this type of treatment is limited. [Abstract]

Kauer-Sant'Anna M, Tramontina J, Andreazza AC, Cereser K, da Costa S, Santin A, Yatham LN, Kapczinski F
Traumatic life events in bipolar disorder: impact on BDNF levels and psychopathology.
Bipolar Disord. 2007 Jun;9 Suppl 1128-35.
BACKGROUND: There is evidence that vulnerability to depression and anxiety disorders is markedly increased by traumatic life events. While childhood abuse has been reported to be associated with poorer outcomes in bipolar disorder, little is known about the neurobiological basis underlying this association. The aim of this study was to ascertain whether bipolar patients who were exposed to a traumatic event or events (TE) have lower brain-derived neurotrophic factor (BDNF) levels and more severe psychopathology as indicated by increased comorbidity and other clinical features when compared to those who were not exposed to TE. METHODS: One-hundred and sixty-three consecutively recruited bipolar outpatients were assessed by Structured Clinical Interview for DSM-IV (SCID) and standard protocol in order to evaluation psychopathology and clinical features. The reported TE was assessed using DSM-IV stem criteria for trauma (as defined by A1 and A2 criteria for trauma for post-traumatic stress disorder). Subjects were divided into 2 groups according to presence or absence of lifetime TE. The levels of BDNF, comorbidity and other clinical features were compared between groups. RESULTS: After adjusting for confounders, results indicated that bipolar patients with a history of TE have alcohol abuse/dependence (p < 0.001), anxiety comorbidity, and lower levels of serum BDNF (p < 0.01) compared to those without a history of TE. There was no difference between the 2 groups in age of onset, presence of psychosis, other substance abuse and dependence, rapid cycling or suicide attempts. CONCLUSIONS: Our findings suggest that TE are associated with significantly increased prevalence of alcohol and anxiety comorbidity as well as lower BDNF levels in bipolar patients. It is possible that a decrease in BDNF levels may account for increased comorbidity, but further prospective studies are required to confirm this. [Abstract]

S� MJ
Psychological aspects of multiple sclerosis.
Clin Neurol Neurosurg. 2007 Nov 16;
A significant incidence and prevalence of psychological disorders in multiple sclerosis (MS) has been reported. Their underlying mechanisms and the extent to which they are reactive to psychosocial factors or symptoms of the pathological process itself, remain unclear. Depression is the predominant psychological disturbance with lifetime prevalence around 50% and annual prevalence of 20%. Depression is commoner during relapses, may exacerbate fatigue and cognitive dysfunction and no firm evidence exists of its induction by interferon; instead, treating depression improves adherence to disease-modifying drugs. Anxiety is also frequent, occurs in newly diagnosed patients, and its co-morbidity with depression has been suggested to increase the rate of suicidal ideation. The relationship between stress and MS is an attractive issue because some studies pointed to an association between stressful life-events and MS onset/relapses; however, the evidence supporting this hypothesis is not conclusive so far. Other psychiatric illnesses, as bipolar affective disorder, pathological laughing and crying or psychosis occur less frequently in MS. Therapeutic strategies include psychotherapy, cognitive behavioural therapy, strengthen of coping, and specific medications. The "art" of the MS team in providing the best individualized care is emphasized, aiming to reduce the burden of the disease and improve the patients' quality of life. [Abstract]

Nierenberg AA, Alpert JE, Gaynes BN, Warden D, Wisniewski SR, Biggs MM, Trivedi MH, Barkin JL, Rush AJ
Family history of completed suicide and characteristics of major depressive disorder: A STAR()D (sequenced treatment alternatives to relieve depression) study.
J Affect Disord. 2007 Nov 13;
BACKGROUND: Clinicians routinely ask patients with non-psychotic major depressive disorder (MDD) about their family history of suicide. It is unknown, however, whether patients with a family member who committed suicide differ from those without such a history. METHODS: Patients were recruited for the STAR()D multicenter trial. At baseline, patients were asked to report first-degree relatives who had died from suicide. Differences in demographic and clinical features for patients with and without a family history of suicide were assessed. RESULTS: Patients with a family history of suicide (n=142/4001; 3.5%) were more likely to have a family history of MDD, bipolar disorder, or any mood disorder, and familial substance abuse disorder, but not suicidal thoughts as compared to those without such a history. The group with familial suicide had a more pessimistic view of the future and an earlier age of onset of MDD. No other meaningful differences were found in depressive symptoms, severity, recurrence, depressive subtype, or daily function. CONCLUSIONS: A history of completed suicide in a family member was associated with minimal clinical differences in the cross-sectional presentation of outpatients with MDD. Limitations of the study include lack of information about family members who had attempted suicide and the age of the probands when their family member died. STARD assessments were limited to those needed to ascertain diagnosis and treatment response and did not include a broader range of psychological measures. [Abstract]

Kim S, Choi KH, Baykiz AF, Gershenfeld HK
Suicide candidate genes associated with bipolar disorder and schizophrenia: An exploratory gene expression profiling analysis of post-mortem prefrontal cortex.
BMC Genomics. 2007 Nov 12;8(1):413.
ABSTRACT: BACKGROUND: Suicide is an important and potentially preventable consequence of serious mental disorders of unknown etiology. Gene expression profiling technology provides an unbiased approach to identifying candidate genes for mental disorders. Microarray studies with post-mortem prefrontal cortex (Brodmann's Area 46/10) tissue require larger sample sizes due to the small magnitude of differentially expressed genes, the genetic heterogeneity of mental disorders, and the mixed cellularity of brain tissue. This study poses the question: to what extent are differentially expressed genes for suicide a diagnostic specific set of genes (bipolar disorder vs. schizophrenia) vs. a shared common pathway? RESULTS: In a reanalysis of a large set of Affymetrix Human Genome U133A microarray data, gene expression levels were compared between suicide completers vs. non-suicide groups within a diagnostic group, namely Bipolar disorder (N=45; 22 suicide completers; 23 non-suicide) or Schizophrenia (N=45; 10 suicide completers ; 35 non-suicide). Among bipolar samples, 13 genes were found and among schizophrenia samples, 70 genes were found as differentially expressed. Two genes, PLSCR4 (phospholipid scramblase 4) and EMX2 (empty spiracles homolog 2 (Drosophila)) were differentially expressed in suicide groups of both diagnostic groups by microarray analysis. CONCLUSIONS: This molecular level analysis suggests that diagnostic specific genes predominate to shared genes in common among suicide vs. non-suicide groups. These differentially expressed, candidate genes are neural correlates of suicide, not necessarily causal. While suicide is a complex endpoint with many pathways, these candidate genes provide entry points for future studies of molecular mechanisms and genetic association studies to test causality. [Abstract]

Tondo L, Lepri B, Baldessarini RJ
Suicidal risks among 2826 Sardinian major affective disorder patients.
Acta Psychiatr Scand. 2007 Dec;116(6):419-28.
OBJECTIVE: We estimated risks of suicidal behaviors in 2826 mood-disorder patients evaluated and followed in a Sardinian mood disorders research center over the past 30 years. METHOD: We determined rates of suicidal ideation, attempts, and suicides, with associated risk factors, in men and women with DSM-IV bipolar I (BP-I; n = 529), BP-II; (n = 314), or major depressive disorders (MDD; n = 1983), at risk for an average of 11 years of illness. RESULTS: Observed rates (% of patients/year) of suicide ranked: BP-II (0.16) > or = BP-I (0.14) > MDD (0.05); attempts: BP-I (1.52) > BP-II (0.82) > MDD (0.48); ideation: BP-II (42.7) > MDD (33.8) > BP-I (22.7). The ratio of attempts/suicides (lethality index) ranked: BP-II (5.12) < MDD (9.60) < or = BP-I (10.8). Male/female risk-ratios were greater for suicide than attempts or ideation. One-third of all reported acts occurred within the first year of illness, and earliest among MDD patients. Factors associated independently with suicidal acts included BP diagnosis, hospitalizations/person, and early illness-onset; factors associated with suicidal ideation were having an affective temperament, BP-II diagnosis, and higher suicidality-corrected depression score at intake. CONCLUSION: Suicidal behaviors were more prevalent among BPD than MDD out-patients. [Abstract]

Akiskal H
Targeting suicide prevention to modifiable risk factors: has bipolar II been overlooked?
Acta Psychiatr Scand. 2007 Dec;116(6):395-402. [Abstract]

Yen CF, Chen CS, Yen JY, Ko CH
The predictive effect of insight on adverse clinical outcomes in bipolar I disorder: A two-year prospective study.
J Affect Disord. 2007 Nov 9;
Research has revealed that a lack of insight is associated with poorer clinical outcomes in schizophrenia; however, the predictive value of insight on adverse clinical outcomes among bipolar patients is quite understudied. The aim of this prospective study was to examine the impact of insight on adverse clinical outcomes among the patients with bipolar I disorder over a 2-year period. Sixty-five remitted bipolar I disorder patients received follow-up assessments at 3, 6, 9, 12, 18, and 24 months to detect the adverse clinical outcomes defined by the incidence of bipolar-related psychiatric hospitalization, emergency room visits, violent or suicidal behavior. The Schedule of Assessment of Insight was used to provide a baseline insight score. Cox regression analysis was used to examine the predictive value of insight on the adverse clinical outcomes. Impaired insight into treatment and a greater number of previous hospitalizations significantly increased the risk of adverse clinical outcomes with bipolar disorder in the 2-year period. However, insight into recognition of the illness and re-labeling of psychotic phenomena did not have any significant effect on adverse clinical outcomes. Bipolar patients' insight into treatment is an independent predictor of adverse clinical outcomes. Improving insight into treatment might be a promising target for a better outcome. [Abstract]

Perroud N, Baud P, Preisig M, Etain B, Bellivier F, Favre S, Reber N, Ferrero F, Leboyer M, Malafosse A
Social phobia is associated with suicide attempt history in bipolar inpatients.
Bipolar Disord. 2007 Nov;9(7):713-21.
Objectives: In an attempt to reduce the phenotypical heterogeneity in an ongoing genetic study of suicidal behavior, we investigated the impact of comorbid anxiety disorders on suicidal behavior in bipolar disorder (BD) patients. Methods: Anxiety disorders were compared in 406 BD I and BD II patients with or without lifetime history of suicide attempt. Results: Among anxiety disorders, only social phobia (SP) was significantly associated with history of suicide attempt in BD [p < 0.001, odds ratio 4.26 (2.284-7.946)]. Moreover, onset of SP was found to precede onset of BD. Conclusions: This result suggests that SP is an important risk factor for suicidal behavior in BD. Further studies are required to determine whether comorbid SP may help to identify a more homogeneous BD sub-group, especially when studies of suicidal behavior are conducted. A second question is whether SP identifies a sub-group of subjects with BD who have a more severe illness course and whether treatment of SP with selective serotonin reuptake inhibitor (SSRI) antidepressants is associated with improvement or worsening of the course of BD. [Abstract]

Etain B, Roy I, Henry C, Rousseva A, Sch�rhoff F, Leboyer M, Bellivier F
No evidence for physical anhedonia as a candidate symptom or an endophenotype in bipolar affective disorder.
Bipolar Disord. 2007 Nov;9(7):706-12.
Objectives: Bipolar affective disorder (BPAD) is clinically and genetically heterogeneous and the affected phenotype is poorly defined, hampering studies of its genetic basis. Studies of specific, familial, clinical indicators of BPAD may be useful for identifying heritable forms. Homogeneous forms of the disease may be identified in patients (candidate symptom approach) and some vulnerability markers may be sought in unaffected relatives of patients (intermediate traits or endophenotypes). Physical anhedonia (PA) is considered a possible candidate symptom and endophenotype in schizophrenia, but has never been specifically investigated in BPAD. Methods: Physical anhedonia scores (measured using Chapman's Physical Anhedonia Scale) were compared in 351 euthymic bipolar patients, 130 of their first-degree relatives and 170 healthy controls with no personal or familial history of schizophrenia, mood disorders or suicidal behavior. We investigated intrafamilial resemblance of PA and compared the progressive and clinical characteristics of hedonic and anhedonic bipolar probands. Results: Physical anhedonia was a stable trait in normothymic bipolar patients and significant intrafamilial correlation of PA scores was observed in bipolar families. However, PA scores were similar in unaffected relatives and controls and the clinical characteristics of anhedonic and hedonic patients did not differ significantly. Physical anhedonia was not associated with an increased familial risk for bipolar disorder. Conclusions: Physical anhedonia is a stable, familial dimension in BPAD families. It cannot be considered an endophenotype because unaffected relatives of bipolar patients and healthy controls have similar PA scores. It also cannot be considered a candidate symptom because it does not identify a homogeneous clinical and familial sub-group of bipolar patients. Given the results of previous studies, PA might be a specific candidate symptom (and endophenotype) to schizophrenia. However, the validation of this hypothesis requires replication studies in bipolar disorder and schizophrenia and further investigations in other psychiatric diseases (in particular across the mood disorder spectrum). [Abstract]

G�bor G
[Investigation of the genetic background of bipolar disorder and schizophrenia (introduction)]
Neuropsychopharmacol Hung. 2007 Jun;9(2):77-9.
The hereditability of bipolar disorder (Bpd) and schizophrenia (Sch) is a well known fact, twin studies are applied to estimate the contribution of the genetic background. Gene linkage studies provided from suicidal brain samples are used to identify mutation of susceptibility genes involved in the etiology. Numerous genes are playing role in the altered signal transduction pathways. Based on the combined effects and functional interactions between the enzymes expressed by these key genes, it could be possible to estimate the genetic risk. Through targeting the intracellular enzymes we can affect the pathogenesis and modify neuronal plasticity of Bpd and Sch, thus developing new psychoactive drugs. [Abstract]

Rihmer Z, D�me P, Gonda X, Kiss HG, Kov�cs D, Seregi K, Teleki Z
Cigarette smoking and suicide attempts in psychiatric outpatients in Hungary.
Neuropsychopharmacol Hung. 2007 Jun;9(2):63-7.
BACKGROUND: Epidemiological and clinical studies have found a significant association between smoking and suicidal behaviour. METHOD: 334 outpatients with DSM-IV diagnosis of unipolar major depression, bipolar (I+II) disorder, schizophrenia, schizoaffective disorder and pure panic disorder were interviewed regarding to their smoking habits and previous suicide attempts. RESULTS: With the exception of panic disorder patients, the rate of prior suicide attempt(s) was much higher among current and lifetime smokers than among never smokers in all diagnostic groups, but the difference was statistically significant only for lifetime smoker unipolar depressives and for current and lifetime smoker schizophrenics. LIMITATIONS: Age, social class and alcohol/caffeine consumption was not controlled and dependent vs nondependent smokers were not distinguished. CONCLUSIONS: The findings support previous results on the strong relationship between smoking and suicidal behaviour in psychiatric (particularly major depressive and schizophrenic) patients. [Abstract]

Tanaka T, Inoue T, Suzuki K, Kitaichi Y, Masui T, Denda K, Koyama T
[Clinical relevance of antidepressant-induced activation syndrome: from a perspective of bipolar spectrum disorder]
Seishin Shinkeigaku Zasshi. 2007;109(8):730-42.
Recent concerns have been raised regarding whether antidepressants, especially selective serotonin reuptake inhibitors (SSRIs) might increase suicidal tendencies and intense debate-rages over the pros and cons of their use. Although systematic reviews and population-based studies have been conducted, a consensus on this association remains to be established. Subsequently, the concept of so-called 'activation syndrome' associated with antidepressants has been accepted without its adequate verification. In the present report, we present our experience of seven cases considered of having 'activation syndrome' brought on by antidepressants, and examine its clinical relevance to bipolar spectrum disorder (Ghaemi, et al., 2001) both symptomatologically and diagnostically. Five patients, diagnosed as having major depressive disorder according to the diagnostic manual (DSM-IV), met the criteria of bipolar spectrum disorder and suffered from activation syndrome following the administration of SSRIs, mainly paroxetine. Similarly, hypomania developed in all five cases with depression; the diagnostic criteria of a hypomanic episode were not met. In the remaining two patients, who were both diagnosed with bipolar disorder, one showed irritability and insomnia through imipramine use, and the another developed a hypomanic and/or a mixed state after the co-administration of fluvoxamine and trazodone. From the results of our examination, 'bipolarity', which is the pivotal factor of bipolar spectrum, might exist behind the phenomenon recognized as activation syndrome, and be revealed by antidepressant treatment, just like manic switching. Moreover, the various problems encountered in the current practice of treating mood disorders, including unipolar-bipolar dichotomy, manic switching by antidepressants, and narrow criteria for a mixed episode, were pointed out a new through this concept of activation syndrome. Actually, the understanding of activation syndrome clinically leads to the prevention of suicidal behavior and the careful use of antidepressants for bipolar (spectrum) disorder, but we must be prudent when applying this concept, since it has not yet been established. [Abstract]

Wilson ST, Stanley B, Oquendo MA, Goldberg P, Zalsman G, Mann JJ
Comparing impulsiveness, hostility, and depression in borderline personality disorder and bipolar II disorder.
J Clin Psychiatry. 2007 Oct;68(10):1533-9.
OBJECTIVE: To determine whether borderline personality disorder (BPD) and bipolar II disorder can be differentiated from each other and from major depressive disorder (MDD) by comparing depression severity, impulsiveness, and hostility in mood disorder patients with and without BPD. METHOD: One hundred seventy-three patients with either MDD or bipolar II disorder were enrolled from a larger sample admitted to a multisite project on mood disorders and suicidal behavior conducted from June 1996 through June 2006. Patients were divided into 4 groups: MDD with BPD, MDD without an Axis II diagnosis, bipolar II disorder with BPD, and bipolar II disorder without an Axis II diagnosis. All diagnoses were based on DSM-IV criteria. Depression was assessed using the 17-item Hamilton Rating Scale for Depression (HAM-D) and the self-rated Beck Depression Inventory (BDI). Impulsiveness was assessed using the Barratt Impulsiveness Scale, and hostility was assessed using the Buss-Durkee Hostility Inventory. RESULTS: Patients with BPD reported higher levels of impulsiveness (p = .004) and hostility (p = .001), independent of Axis I diagnosis. Bipolar II patients reported greater attentional impulsiveness (p = .008) than MDD patients, independent of BPD status, while BPD patients reported greater nonplanning impulsiveness than patients without BPD, independent of Axis I diagnosis (p = .02). For motor impulsiveness, there was a main effect for Axis I diagnosis (p = .05) and Axis II diagnosis (p = .002). The bipolar II + BPD group scored the highest, suggesting a compound effect of comorbidity. There were no differences in depression severity when measured with the HAM-D, although the BPD groups reported more severe depression on the BDI, independent of their Axis I diagnosis (p = .05). The BPD groups scored higher on the cognitive factor (p = .01) and anxiety factor (p = .03) of the HAM-D. CONCLUSION: Results suggest that there is a unique symptom and trait profile associated with BPD that distinguishes the diagnosis from bipolar II disorder. Results also suggest that impulsiveness is an important aspect of both disorders and that there is a compounding effect associated with a diagnosis of bipolar II disorder with comorbid BPD. [Abstract]

Romero S, Colom F, Iosif AM, Cruz N, Pacchiaroti I, Sanchez-Moreno J, Vieta E
Relevance of family history of suicide in the long-term outcome of bipolar disorders.
J Clin Psychiatry. 2007 Oct;68(10):1517-21.
OBJECTIVE: This study examined the association between family history of completed suicide and suicidal behavior and other clinical variables in subjects with bipolar disorder. METHOD: 374 outpatients aged from 19 to 88 years (mean +/- SD age = 41.9 +/- 4.1 years) (54.3% female) meeting DSM-IV criteria for bipolar disorder type I or II or schizoaffective disorder, bipolar subtype, were included in the study. Forty-eight subjects with a family history of completed suicide were compared to 326 subjects without a family history of completed suicide regarding several clinical and demographic variables. The study was conducted from 2001 to 2004. RESULTS: There were no statistically significant demographic differences between bipolar disorder subjects with and without a family history of suicide. Bipolar disorder subjects with a family history of suicide showed higher rates of cluster C personality disorders than subjects without a family history of suicide (14.9% vs. 2.5%, OR = 6.72, 95% CI = 2.31 to 19.51, p < .001). Subjects with a family history of suicide also demonstrated a significantly greater lifetime prevalence of suicide attempts (52.2% vs. 25.5%, OR = 3.19, 95% CI = 1.7 to 6.0, p < .001). Results remained significant after controlling for all possible interactions. CONCLUSION: Family history of completed suicide is a significant risk factor associated with suicidal attempts in patients with bipolar disorder. These findings underscore the importance of identifying patients with a family history of suicide in order to provide prompt treatment and careful follow-up. [Abstract]

Goldberg JF, McElroy SL
Bipolar mixed episodes: characteristics and comorbidities.
J Clin Psychiatry. 2007 Oct;68(10):e25.
Mixed episodes are associated with greater total lifetime costs, increased suicide risk, and increased substance misuse than pure manic episodes and may resemble depressive episodes due to similar quality of life scores, cognitive styles, and likelihood of cycling to depression. Patients with mixed states have an increased potential for abnormally low cholesterol, hypothyroidism, and other medical comorbidities that can slow recovery. In addition, patients with mixed states can have comorbid anxiety disorders and ADHD. [Abstract]

Skale TG, Jain R
Practical strategies for assessing and stabilizing bipolar patients in urgent situations.
J Clin Psychiatry. 2007 Oct;68(10):e23.
For patients with bipolar disorder in urgent situations, psychiatric and nonpsychiatric clinicians should employ practical approaches to achieve optimum outcomes and ensure safe and rapid reduction of symptoms, such as considering the treatment setting, clinician-patient relationship, and the severity of the patient's symptoms. Because biological, psychological, and social factors affect both the development and the treatment of acute bipolar states, treatment should address each factor to manage the illness. [Abstract]

M�ller-Oerlinghausen B
[Pharmacological suicide prevention under special consideration of lithium salts]
Psychiatr Prax. 2007 Sep;34 Suppl 3S292-5.
OBJECTIVE: This minireview summarizes the existing evidence from large, international observational studies and RCTs on the suicide preventive effects of lithium as compared to other mood stabilizers and antidepressants. METHODS: Unsystematic literature review. RESULTS: There is increasing and robust evidence from a relatively large number of studies and metaanalyses that lithium long-term treatment reduces the suicide risk and overall mortality in patients with all kinds of depressive disorders (unipolar, bipolar, schizoaffective). Comparable evidence does not exist with regard to other mood stabilizers including atypical neuroleptics, or antidepressants. CONCLUSIONS: The existing evidence on the suicide preventive effect of lithium should be integrated in therapeutic guidelines and routine psychiatric care. [Abstract]

Bond DJ, Pratoomsri W, Yatham LN
Depot antipsychotic medications in bipolar disorder: a review of the literature.
Acta Psychiatr Scand Suppl. 2007;(434):3-16.
OBJECTIVE: To review the literature on the efficacy and safety of depot formulations of first- and second-generation antipsychotic medications (FGAs and SGAs) in patients with bipolar disorder. METHOD: We conducted a computer-aided MEDLINE search using the search terms 'depot antipsychotic', 'bipolar disorder' and 'compliance.' RESULTS: We identified eight published reports in bipolar patients regarding the use of depot FGAs, and six preliminary reports on the use of depot SGAs. These studies suggest that depots FGAs are efficacious in preventing manic episodes during the maintenance treatment of bipolar disorder. Several studies, however, indicate that depot FGAs may be associated with increased time with depressive symptoms, particularly in patients with a predominantly depressive course of illness. Preliminary data on the role of depot formulations of SGAs suggest that they reduce the frequency of both manic and depressive episodes during maintenance treatment, and are well tolerated by patients. CONCLUSION: After a careful risk-benefit analysis, depot antipsychotics may be considered for the long-term control of mood episodes in bipolar patients who have relapsed due to medication non-adherence or who have failed to respond to standard therapies. Depot FGAs should be avoided in patients with a high burden of illness from depressive symptoms and particularly in those judged to be at high risk of suicide. The available data on depot formulations of SGAs indicate that they are efficacious in the maintenance treatment of bipolar illness without increasing the burden of the depressive pole of the illness, but further systematic studies are required to definitively assess this. [Abstract]

Sakurai K, Nishiguchi N, Shirakawa O, Nushida H, Ueno Y, Maeda K, Hayashi Y
Lack of Association between Endoplasmic Reticulum Stress Response Genes and Suicidal Victims.
Kobe J Med Sci. 2007;53(4):151-5.
As lithium has been shown to have a protective effect against suicidal behavior, genes on which mood stabilizers act may be involved in biological susceptibility to suicide. A recent study showed that endoplasmic reticulum (ER) stress response was impaired in the bipolar disorders and the impairment was ameliorated by a mood stabilizer, valproate. We hypothesized that an alteration of ER stress response is involved in the biological susceptibility to suicide through genetic polymorphisms, and examined the association of polymorphisms of X-box binding protein 1 (XBP1) and heat shock 70-kDa protein 5 (HSPA5) genes with suicide. We found no significant difference in the distribution of these polymorphisms between the suicide victims and the controls. These results suggest that the polymorphisms examined in this study are not involved in the susceptibility to suicide of the Japanese. [Abstract]

Fountoulakis KN, Vieta E, Siamouli M, Valenti M, Magiria S, Oral T, Fresno D, Giannakopoulos P, Kaprinis GS
Treatment of bipolar disorder: a complex treatment for a multi-faceted disorder.
Ann Gen Psychiatry. 2007;627.
ABSTRACT: BACKGROUND: Manic-depression or bipolar disorder (BD) is a multi-faceted illness with an inevitably complex treatment. METHODS: This article summarizes the current status of our knowledge and practice of its treatment. RESULTS: It is widely accepted that lithium is moderately useful during all phases of bipolar illness and it might possess a specific effectiveness on suicidal prevention. Both first and second generation antipsychotics are widely used and the FDA has approved olanzapine, risperidone, quetiapine, ziprasidone and aripiprazole for the treatment of acute mania. These could also be useful in the treatment of bipolar depression, but only limited data exists so far to support the use of quetiapine monotherapy or the olanzapine-fluoxetine combination. Some, but not all, anticonvulsants possess a broad spectrum of effectiveness, including mixed dysphoric and rapid-cycling forms. Lamotrigine may be effective in the treatment of depression but not mania. Antidepressant use is controversial. Guidelines suggest their cautious use in combination with an antimanic agent, because they are supposed to induce switching to mania or hypomania, mixed episodes and rapid cycling. CONCLUSION: The first-line psychosocial intervention in BD is psychoeducation, followed by cognitive-behavioral therapy. Other treatment options include Electroconvulsive therapy and transcranial magnetic stimulation. There is a gap between the evidence base, which comes mostly from monotherapy trials, and clinical practice, where complex treatment regimens are the rule. [Abstract]

Neves FS, Correa HH
Is smoking associated with suicide in bipolar patients?
J Clin Psychiatry. 2007 Sep;68(9):1446-7; author reply 1447-8. [Abstract]

Ostacher MJ, Nierenberg AA, Perlis RH, Eidelman P, Borrelli DJ, Tran TB, Marzilli Ericson G, Weiss RD, Sachs GS
The relationship between smoking and suicidal behavior, comorbidity, and course of illness in bipolar disorder.
J Clin Psychiatry. 2006 Dec;67(12):1907-11.
OBJECTIVES: The rate of smoking in people with bipolar disorder is much greater than in the general population, but the implications of smoking for the course of bipolar disorder have not been well studied. The purpose of this retrospective study was to examine the relationship between smoking, severity of bipolar disorder, suicidal behavior, and psychiatric and substance use disorder comorbidity. METHOD: We evaluated 399 outpatients with bipolar disorder who were treated in a bipolar specialty clinic from December 1999 to October 2004. Diagnosis, mood state, course of illness, functioning, and psychiatric comorbidities were assessed using the Affective Disorders Evaluation and the Mini-International Neuropsychiatric Interview. RESULTS: Of the 399 patients evaluated, 155 (38.8%) had a history of daily smoking. Having ever smoked was associated with earlier age at onset of first depressive or manic episode, lower Global Assessment of Functioning scores, higher Clinical Global Impressions-Bipolar Disorder scale scores, lifetime history of a suicide attempt (47% for smokers vs. 25% for those who had never smoked), and lifetime comorbid disorders: anxiety disorders, alcohol abuse and dependence, and substance abuse and dependence. In a logistic regression model including these factors, suicide attempts and substance dependence were significantly associated with smoking in patients with bipolar disorder. CONCLUSIONS: Bipolar patients with lifetime smoking were more likely to have earlier age at onset of mood disorder, greater severity of symptoms, poorer functioning, history of a suicide attempt, and a lifetime history of comorbid anxiety and substance use disorders. Smoking may be independently associated with suicidal behavior in bipolar disorder. [Abstract]

Cerullo MA, Strakowski SM
The prevalence and significance of substance use disorders in bipolar type I and II disorder.
Subst Abuse Treat Prev Policy. 2007;229.
ABSTRACT: The aim of this paper is to provide a systematic review of the literature examining the epidemiology, outcome, and treatment of patients with bipolar disorder and co-occurring substance use disorders (SUDs). Articles for this review were initially selected via a comprehensive Medline search and further studies were obtained from the references in these articles. Given the lack of research in this field, all relevant studies except case reports were included.Prior epidemiological research has consistently shown that substance use disorders (SUDs) are extremely common in bipolar I and II disorders. The lifetime prevalence of SUDs is at least 40% in bipolar I patients. Alcohol and cannabis are the substances most often abused, followed by cocaine and then opioids. Research has consistently shown that co-occurring SUDs are correlated with negative effects on illness outcome including more frequent and prolonged affective episodes, decreased compliance with treatment, a lower quality of life, and increased suicidal behavior. Recent research on the causal relationship between the two disorders suggests that a subgroup of bipolar patients may develop a relatively milder form of affective illness that is expressed only after extended exposure to alcohol abuse.There has been very little treatment research specifically targeting this population. Three open label medication trials provide limited evidence that quetiapine, aripiprazole, and lamotrigine may be effective in treating affective and substance use symptoms in bipolar patients with cocaine dependence and that aripiprazole may also be helpful in patients with alcohol use disorders. The two placebo controlled trials to date suggest that valproate given as an adjunct to lithium in bipolar patients with co-occurring alcohol dependence improves both mood and alcohol use symptoms and that lithium treatment in bipolar adolescents improves mood and SUD symptoms.Given the high rate of SUD co-occurrence, more research investigating treatments in this population is needed. Specifically, double blind placebo controlled trials are needed to establish the effectiveness of medications found to be efficacious in open label treatments. New research also needs to be conducted on medications found to treat either bipolar disorder or a SUD in isolation. In addition, it may be advisable to consider including patients with prior SUDs in clinical trials for new medications in bipolar disorder. [Abstract]

Soares-Weiser K, Bravo Vergel Y, Beynon S, Dunn G, Barbieri M, Duffy S, Geddes J, Gilbody S, Palmer S, Woolacott N
A systematic review and economic model of the clinical effectiveness and cost-effectiveness of interventions for preventing relapse in people with bipolar disorder.
Health Technol Assess. 2007 Oct;11(39):1-226.
OBJECTIVES: To determine the clinical effectiveness and cost-effectiveness of pharmacological and/or psychosocial interventions for the prevention of relapse in people with bipolar disorder. DATA SOURCES: Major electronic databases were searched up to September 2005. REVIEW METHODS: Systematic reviews were undertaken on the clinical and economic effectiveness of treatments. An analysis was performed using the methods of mixed treatment comparison (MTC) to enable indirect comparisons to be made between the treatments. An economic model of treatments for the prevention of relapse in bipolar disorder was developed. RESULTS: Forty-five trials were included in the clinical effectiveness review; all but one studied adults. This review found that for the prevention of all relapses, lithium, valproate, lamotrigine and olanzapine performed better than placebo, with lithium and lamotrigine having the strongest evidence. For depressive relapse prevention, valproate, lamotrigine and imipramine performed better than placebo, with evidence strongest for lamotrigine and weakest for imipramine. For manic relapses, lithium and olanzapine performed significantly better than placebo. The MTC found that the best treatment for bipolar I patients with mainly depressive symptoms was valproate, followed by lithium plus imipramine. For bipolar I patients with mainly manic symptoms, olanzapine was the best treatment. From the studies investigating psychosocial interventions, there were few data for each comparison and outcome. The evidence suggests that cognitive behaviour therapy (CBT), in combination with usual treatment, is effective for the prevention of relapse. Group psychoeducation and possibly family therapy may also have roles as adjunctive therapy for preventing relapse. The results from the decision analytic model developed on the cost-effectiveness of long-term maintenance treatments of bipolar I patients suggest that the choice of treatment is dependent upon a number of factors: the previous episode history of a patient and the mortality benefit assumed for lithium strategies. The results from the base-case analysis for patients with a recent history of depression suggest that valproate, lithium and the combination of lithium and imipramine are potentially cost-effective depending upon the amount that a decision-maker is willing to pay for additional health gain. Using conventional amounts that the NHS is prepared to pay for health gain, then the lithium-based strategies appear to be potentially cost-effective for this group. For patients with a recent history of mania, the choice of pharmacological intervention appears to be between olanzapine and lithium monotherapy. Again using conventional threshold as a reference point, the results suggest that lithium is the most cost-effective therapy. Excluding the additional mortality benefit associated with lithium-based strategies resulted in all treatments for patients with a recent history of a depressive episode being dominated by valproate and, in the case of patients with a recent history of a manic episode, by olanzapine. CONCLUSIONS: Lithium, valproate, lamotrigine and olanzapine are effective as maintenance therapy for the prevention of relapse in bipolar disorder. Olanzapine and lithium are efficacious for the prevention of manic relapses and valproate, lamotrigine and imipramine for the prevention of depressive relapse. There is some evidence that CBT, group psychoeducation and family therapy might be beneficial as adjuncts to pharmacological maintenance treatments. Insufficient information is