New anticonvulsant medication uses in bipolar disorder

Therapy of bipolar disorders is a rapidly evolving field. Lithium has efficacy in classic bipolar disorders whereas divalproex sodium and carbamazepine may have broader spectrum efficacy that includes non-classic bipolar disorder. In the last 10 years, a series of anticonvulsants have been approved for marketing in the United States. Gabapentin has indirect g-aminobuytric acid-ergic actions, is generally well tolerated, and appears to have anxiolytic, analgesic, and hypnotic effects. Lamotrigine has antiglutamatergic actions and is generally well tolerated (aside from rash in 1 in 10, and serious rash in 1 in 1,000 patients). Lamotrigine is indicated for maintenance treatment in bipolar disorder. Emerging evidence suggests lamotrigine may have utility in bipolar disorder patients with depression and treatment-refractory rapid cycling, as well as analgesic effects. Topiramate and zonisamide may allow both weight loss, while topiramate may have specific efficacy in bulimia, binge eating disorder, and alcohol dependence. Two small studies found oxcarbazepine had similar efficacy to lithium and haloperidol in acute mania. Phenytoin, an older anticonvulsant, may have adjunctive acute mania efficacy. Levetiracetam, a newer anticonvulsant, may be worth exploring and has minimal drug-drug interactions. None of these newer agents has been shown effective in a large placebo controlled trial for acute mania. Although the clinical profiles of these newer anticonvulsants do not appear to overlap markedly with divalproex and carbamazepine (except perhaps for oxcarbazepine), these novel agents may still offer important new options in relieving a variety of specific target symptoms in patients with bipolar disorder.     

Differenzialdiagnose schizoaffektive Störung versus bipolare Störung

This case presentation describes a 22-year-old woman after an episode of psychotic mania. Manic-psychotic and depressive episodes, partially with psychotic symptoms, and different diagnoses have been documented for the past 5 years, raising the question of the differential diagnosis between bipolar disorder and schizoaffective disorder. Depending on the classification (ICD-10 versus DSM-5), schizoaffective disorder is defined differently. According to ICD-10, schizoaffective episodes can be diagnosed when affective and schizophrenic symptoms occur simultaneously. In a different approach, DSM-V requires psychotic symptoms in the absence of major mood episodes for at least 2 weeks in the course of the disorder.     

Cognitive responses to failure and success relate uniquely to bipolar depression versus mania

This project examined cognitive responses to failure and success and their association with depression and mania within bipolar disorder. Many cognitive variables that are associated with unipolar depression have been found to be involved in bipolar disorder, more specifically bipolar depression. This research was the first to examine tendencies to hold high standards, engage in self-criticism, and generalize from failure to an overall sense of self-worth. In Study 1, undergraduates were screened for risk of mood disorders and completed structured diagnostic interviews. History of bipolar spectrum disorders and history of depression had separate associations with negative generalization. The association of generalization with bipolar spectrum disorders was accounted for by current depressive symptoms. For Study 2, the authors developed a measure of the tendency to engage in positive generalization following success experiences. In a sample of 276 undergraduates, this measure related uniquely to risk for mania. Results of these 2 studies suggest that responses to failure are associated with a history of depression, whereas responses to success are associated with a risk for mania. Implications for future research and clinical work are discussed.     

Mental imagery as an emotional amplifier: application to bipolar disorder

Cognitions in the form of mental images have a more powerful impact on emotion than their verbal counterparts. This review synthesizes the cognitive science of imagery and emotion with transdiagnostic clinical research, yielding novel predictions for the basis of emotional volatility in bipolar disorder. Anxiety is extremely common in patients with bipolar disorder and is associated with increased dysfunction and suicidality, yet it is poorly understood and rarely treated. Mental imagery is a neglected aspect of bipolar anxiety although in anxiety disorders such as posttraumatic stress disorder and social phobia focusing on imagery has been crucial for the development of cognitive behavior therapy (CBT).In this review we present a cognitive model of imagery and emotion applied to bipolar disorder. Within this model mental imagery amplifies emotion, drawing on Clark's cyclical panic model [(1986). A cognitive approach to panic. Behaviour Research and Therapy, 24, 461–470]. We (1) emphasise imagery's amplification of anxiety (cycle one); (2) suggest that imagery amplifies the defining (hypo-) mania of bipolar disorder (cycle two), whereby the overly positive misinterpretation of triggers leads to mood elevation (escalated by imagery), increasing associated beliefs, goals, and action likelihood (all strengthened by imagery).Imagery suggests a unifying explanation for key unexplained features of bipolar disorder: ubiquitous anxiety, mood instability and creativity. Introducing imagery has novel implications for bipolar treatment innovation - an area where CBT improvements are much-needed.     

Reassessing carbamazepine in the treatment of bipolar disorder: clinical implications of new data

This monograph summarizes the proceedings of a roundtable meeting convened to discuss the role of carbamazepine in the treatment of bipolar disorder, in light of new data and the recent indication of carbamazepine extended-release capsules (CBZ ERC) for use in the treatment of acute manic and mixed episodes. Two lectures were presented, followed by a panel discussion among all 6 participants. A summary of the two pivotal trials of CBZ ERC and their pooled data along with other relevant data is presented first. Next, historical trends of carbamazepine and the agent's use in acute mania, bipolar depression, and maintenance are reviewed, emphasizing clinical implications of efficacy, safety, tolerability, and drug interactions. Finally, the panel discussion provides recommendations for the use of carbamazepine in different phases of the illness, taking into account adverse effects and drug-drug interactions. Panel discussants agree that current data confirm the utility of CBZ ERC as an effective treatment for acute manic and mixed episodes in bipolar disorder. Carbamazepine may also prove to be an option for maintenance treatment. Tolerability of the drug is related to dose and titration, and overall safety limitations regarding carbamazepine usage are comparable to other medications. For some patients, the main challenges to use of carbamazepine may be common drug-drug interactions and increased side effects related to aggressive introduction during treatment of acute manic and mixed episodes. Thus, carbamazepine may be a lower priority option for patients who are taking multiple medications, such as elderly individuals with medical comorbidity, due to the potential for drug interactions. Important benefits of carbamazepine include the low propensity toward weight gain and evidence of good tolerability with long-term treatment. (At present there are no available data from long-term, placebo-controlled studies evaluating the effects of carbamazepine or CBZ ERC on weight.) Thus, carbamazepine may be a good option for patients who are concerned about weight gain or who are intolerant of or respond poorly to other medications. Further efforts are needed to update physicians on the use of carbamazepine relative to other medications in the treatment of bipolar disorder.     

Family Functioning and the Course of Adolescent Bipolar Disorder

The symptoms of bipolar disorder affect and are affected by the functioning of family environments. Little is known, however, about the stability of family functioning among youth with bipolar disorder as they cycle in and out of mood episodes. This study examined family functioning and its relationship to symptoms of adolescent bipolar disorder, using longitudinal measures of family cohesion, adaptability, and conflict. Parent- and adolescent-reported symptom and family functioning data were collected from 58 families of adolescents with bipolar disorder (mean age = 14.48 ± 1.60; 33 female, 25 male) who participated in a 2-year randomized trial of family-focused treatment for adolescents (FFT-A). Cohesion and adaptability scores did not significantly change over the course of the study. Parent-reported conflict prior to psychosocial treatment moderated the treatment responses of families, such that high-conflict families participating in FFT-A demonstrated greater reductions in conflict over time than low-conflict families. Moreover, adolescent mania symptoms improved more rapidly in low-conflict than in high-conflict families. For all respondents, cohesion, adaptability, and conflict were longitudinally correlated with adolescents’ depression scores. Finally, decreases in parent-reported conflict also predicted decreases in adolescents’ manic symptoms over the 2-year study. Findings suggest that family cohesion, adaptability, and conflict may be useful predictors of the course of adolescent mood symptoms. Family conflict may be an important target for family intervention in early onset bipolar disorder.     

Role of Reward Sensitivity and Processing in Major Depressive and Bipolar Spectrum Disorders

Since Costello’s (1972) seminal Behavior Therapy article on loss of reinforcers or reinforcer effectiveness in depression, the role of reward sensitivity and processing in both depression and bipolar disorder has become a central area of investigation. In this article, we review the evidence for a model of reward sensitivity in mood disorders, with unipolar depression characterized by reward hyposensitivity and bipolar disorders by reward hypersensitivity. We address whether aberrant reward sensitivity and processing are correlates of, mood-independent traits of, vulnerabilities for, and/or predictors of the course of depression and bipolar spectrum disorders, covering evidence from self-report, behavioral, neurophysiological, and neural levels of analysis. We conclude that substantial evidence documents that blunted reward sensitivity and processing are involved in unipolar depression and heightened reward sensitivity and processing are characteristic of hypomania/mania. We further conclude that aberrant reward sensitivity has a trait component, but more research is needed to clearly demonstrate that reward hyposensitivity and hypersensitivity are vulnerabilities for depression and bipolar disorder, respectively. Moreover, additional research is needed to determine whether bipolar depression is similar to unipolar depression and characterized by reward hyposensitivity, or whether like bipolar hypomania/mania, it involves reward hypersensitivity.     

The "good enough" mood stabilizer: a review of the clinical evidence

A growing family of medications is used for mood stabilization in bipolar disorder. These medications fall into two broad categories according to likely mechanisms of action. Within the categories, specific drugs may vary in their efficacy for different phases of the disorder. The first category, including lithium, anticonvulsants, and some novel treatments, appears to have mechanisms related to intracellular second messengers. These medications have more pronounced antimanic than antidepressant effects, except for lamotrigine, which has antidepressant effects without precipitating mania. The second group of mood stabilizers is the atypical antipsychotics, which act through dopamine and other monoamines. Olanzapine and in all likelihood other drugs in the class possess marked, acute antimanic properties and possible antidepressant properties, but require further study before they can be used as routine options in long-term care. It is clear that the advent of multiple mood stabilizer candidates has not yet led to a single ideal therapy for bipolar disorder, but rather to options that can be flexibly tailored to the lifetime needs of individual patients, in sequences or combinations, and perhaps in conjunction with other classes of psychotropics.     

Exploring Behavioral Activation and Inhibition Sensitivities Among College Students at Risk for Bipolar Spectrum Symptomatology

We explored cross-sectionally the roles in bipolar spectrum symptomatology of two broad motivational systems that are thought to control levels of responsiveness to cues of threat and reward, the Behavioral Inhibition System (BIS) and the Behavioral Activation System (BAS). Undergraduate students (n = 357) completed questionnaires regarding (a) bipolar spectrum disorders [the General Behavior Inventory (GBI), a well-established clinical screening measure], (b) current depression and mania symptoms (the Internal State Scale; ISS), and (c) BIS/BAS sensitivities (the BIS/BAS scales). Validated cutoff scores on the GBI were used to identify individuals at risk for a mood disorder. It was hypothesized that, among at-risk respondents, high BAS and low BIS levels would be associated with high current mania ratings, whereas low BAS and high BIS would be associated with high current depression ratings. Multiple regression analyses indicated that, among at-risk individuals (n = 63), BAS accounted for 27% of current mania symptoms but BIS did not contribute. For these individuals, BAS and BIS were both significant and together accounted for 44% of current depressive symptoms.     

Cognitive Insight in Inpatients with Psychotic, Bipolar, and Major Depressive Disorders

The Beck Cognitive Insight Scale (BCIS; Beck, Baruch, Balter, Steer, & Warman, 2004) was administered to 42 (28%) inpatients with psychotic disorders, 52 (35%) with a bipolar disorder, and 56 (37%) with a major depressive disorder (MDD). The hypotheses were (a) that the mean level of cognitive insight in a psychotic or a bipolar disorder is lower than that in a MDD, (b) that the mean levels of cognitive insight in psychotic and bipolar disorders were comparable, and (c) that the mean BCIS index score for a bipolar disorder in which the most recent episode had been mania is lower than the mean BCIS index score for a bipolar disorder in which the most recent episode had been mixed or depressed. All three hypotheses were supported. The results were discussed as supporting cognitive insight as a psychological construct that varies predictably according to the nature of a psychiatric disorder.     

A test of the bidirectional association between sleep and mood in bipolar disorder and insomnia

The present study investigates sleep, mood, and the proposed bidirectional relationship between the two in psychiatric disorders. Participants with interepisode bipolar disorder (n = 49), insomnia (n = 34), and no psychiatric history (n = 52) completed seven consecutive days of sleep diaries and mood measures. The interepisode bipolar and insomnia participants exhibited greater sleep disturbance than the healthy control individuals. Negative mood was equally heightened in both interepisode bipolar disorder and insomnia, and there were no differences between the three groups in positive mood. Total wake time was associated with next morning negative mood in bipolar disorder, whereas evening negative mood was associated with subsequent total wake time in both bipolar disorder and insomnia. Additionally, positive mood was associated with subsequent total wake time for the insomnia group. Results support the theory that disruptions in nighttime sleep and daytime mood may be mutually maintaining and suggest the potential importance of transdiagnostic or universal processes.     

Patient preferences for medicine administration for acute agitation: results from an internet-based survey of patients diagnosed with bipolar disorder or schizophrenia in two Nordic countries

The objective was to elicit patient preferences for medicine administration method in the management of acute agitation episodes among patients diagnosed with bipolar disorder or schizophrenia. The patients’ experiences of acute agitation episodes and their management of episodes were also explored. Data were collected via an anonymous, internet-based survey of residents in Denmark or Sweden with schizophrenia or bipolar disorder (October 2014 to December 2014). Inclusion criteria were having a diagnosis of schizophrenia or bipolar disorder, and being above 18 years of age. The questionnaire included questions about preferences for medication attributes, experiences with pharmacological treatment for agitation and involvement in treatment plans. A total of 237 diagnosed patients (61 with schizophrenia; 176 with bipolar disorder) completed the questionnaire. Agitation episodes were experienced by 90% of the respondents. In total, 83% of the respondents reported having received treatment with tablets. When patients were presented with the attributes of an inhalation method, respondents stated that the fast onset of action, low risk of adverse reactions and least invasive form of drug delivery were positive attributes of treatment with inhalation. Inhalation is a new delivery route for treatment of acute agitation in patients diagnosed with bipolar disorder or schizophrenia. Inhalation is the preferred treatment method for acute agitation among Danish and Swedish patients with bipolar disorder or schizophrenia.     

Rapid Cycling

Rapid cycling is not a distinct disorder, but is a particularly severe form of bipolar disease. One in six patients with bipolar disease seen by psychiatrists either as an outpatient or as an inpatient suffers from four or more episodes per year. If at least four episodes occur within one year, this high-frequency phase is called ?rapid cycling“ (RC). Treatment for bipolar disorder with RC usually includes trialling mood stabilizers, such as lithium, anticonvulsants, and modern antipsychotics.In four out of five RC patients, treatment improves disease progression; however, some patients exhibit RC for many years.Specific studies have raised the suspicion that administering antidepressive therapy could facilitate an unfavorable course of bipolar affective disorder. The present case demonstrates disease progression and treatment attempts in a patient with distinct RC progression.     

Rethinking the mood and anxiety disorders: a quantitative hierarchical model for DSM-V

The fourth edition of the Diagnostic and Statistical Manual of Mental Disorders (American Psychiatric Association, 1994) groups disorders into diagnostic classes on the basis of the subjective criterion of "shared phenomenological features." There are now sufficient data to eliminate this rational system and replace it with an empirically based structure that reflects the actual similarities among disorders. The existing structural evidence establishes that the mood and anxiety disorders should be collapsed together into an overarching class of emotional disorders, which can be decomposed into 3 subclasses: the bipolar disorders (bipolar I, bipolar II, cyclothymia), the distress disorders (major depression, dysthymic disorder, generalized anxiety disorder, posttraumatic stress disorder), and the fear disorders (panic disorder, agoraphobia, social phobia, specific phobia). The optimal placement of other syndromes (e.g., obsessive-compulsive disorder) needs to be clarified in future research.     

Assessing the dysregulation of the Behavioral Activation System: the Hypomanic Personality Scale and the BIS-BAS scales

We discuss the Hypomanic Personality Scale (Hyp; Eckblad & Chapman, 1986) and the Behavioral Inhibition System (BIS-BAS; Carver & White, 1994) and Behavioral Activation System (BAS; Gray, 1991) Scales as risk factors for bipolar disorders. The dysregulation of the BAS is considered to be central and results in higher variability in mood. Therefore, we examined how those scales are associated with mood fluctuations. A total of 59 participants completed a diary for at least 17 days. It included a modified Center for Epidemiologic Studies-Depression Scale (Meyer & Hautzinger, 2001) assessing depression and mania and the Positive and Negative Affect Schedule (Watson, Clark, & Tellegen, 1988). Hyp and BAS predicted levels of mania and of positive affect but also fluctuations of mania. Hyp also predicted instability of negative affect. Our data also suggest that mood variability is a trait-like feature. Both scales seem not to be perfect measures of the dysregulation factor. Future research should assess this dysregulation more directly.     

Unique association of approach motivation and mania vulnerability

Bipolar disorder involves experiences of both mania and depression over time, and measures of mania-risk and depression-risk therefore tend to be correlated, making it difficult to disentangle the shared versus unique aspects of mania and depression vulnerability. In theory, strong approach motivation is uniquely linked with mania risk, but this relation tends to be obscured unless co-occurring depression risk is statistically controlled. In this study, 461 college students completed the General Behaviour Inventory (GBI)—a validated questionnaire of bipolar disorder vulnerability—and they reported their degree of approach motivation in response to four vignettes that varied in relative incentive versus threat strength. After controlling for the effect of depression vulnerability, mania vulnerability was associated with approach motivation, particularly in response to more threatening scenarios, and this association remained significant even when controlling for dispositional threat and incentive responsiveness, current symptoms, mood, self-esteem, and optimism. The results are consistent with models that regard heightened approach motivation as a unique aspect of mania vulnerability.     

A longitudinal study of high scorers on the hypomanic personality scale

Former college students (n = 36) identified by high scores on the Hypomanic Personality Scale (HYP; Eckblad & Chapman, 1986) were compared with control participants (n = 31) at a 13-year follow-up assessment. As hypothesized, the HYP group reported more bipolar disorders and major depressive episodes than the control group. The HYP group also exceeded the control group on the severity of psychotic-like experiences, symptoms of borderline personality disorder, and rates of substance use disorders. HYP group members with elevated scores on the Impulsive-Nonconformity Scale (Chapman et al., 1984) experienced greater rates of bipolar mood disorders, poorer overall adjustment, and higher rates of arrest than the remaining HYP or control participants.     

Preventing Mania: A Preliminary Examination of the GOALS Program

There is strong evidence of a relationship between goal dysregulation and mania. Building on these findings, we examined the feasibility of developing a mania prevention treatment program designed to improve goal regulation skills for those with bipolar disorder. Here, we describe the process of developing a manual, delivering the intervention to a series of cases, and then conducting a small open uncontrolled trial. All participants met diagnostic criteria for bipolar I disorder based on the Structured Clinical Interview for DSM-IV and were not currently experiencing episodes of depression or mania. Ten participants (8 female, mean age = 46.7 years) were enrolled in the GOALS program and completed an average of 13.2 weekly sessions. Participants were administered the Bech-Rafaelson Mania Scale (BRMS) and the Modified Hamilton Rating Scale for Depression at baseline and termination. Some participants completed self-report scales including the Altman Self-Rating Mania Scale, the Beck Depression Inventory, and the Willingly Approached Set of Statistically Unrealistic Pursuits at baseline and termination. In addition, participants were administered a consumer satisfaction questionnaire at termination. At termination, all 10 participants found the program highly relevant and helpful. Most importantly, even though levels of mania were low initially, mean levels of manic symptoms on the BRMS decreased significantly from baseline to termination, and all 10 participants were within a healthy range (BRMS < 7) at termination. Although the lack of control group or follow-up data limits this study, preliminary evidence suggests that it is feasible to identify treatment targets by drawing from the basic research literature in bipolar disorder. Findings await replication and more careful testing within a randomized controlled trial.