S. N. Ghaemi

Long-term antidepressant treatment in bipolar disorder: meta-analyses of benefits and risks

Objective:  Long‐term antidepressant (AD) treatment for depression in bipolar disorder (BPD) patients is highly prevalent, but its benefits and risks remain uncertain, encouraging this meta‐analysis of available research.

Antidepressant discontinuation in bipolar depression: a Systematic Treatment Enhancement Program for Bipolar Disorder (STEP-BD) randomized clinical trial of long-term effectiveness and safety.

OBJECTIVE To assess long-term effectiveness and safety of randomized antidepressant discontinuation after acute recovery from bipolar depression. METHOD In the Systematic Treatment Enhancement Program for Bipolar Disorder (STEP-BD) study, conducted between 2000 and 2007, 70 patients with DSM-IV-diagnosed bipolar disorder (72.5% non-rapid cycling, 70% type I) with acute major depression, initially responding to treatment with antidepressants plus mood stabilizers, and euthymic for 2 months, were openly randomly assigned to antidepressant continuation versus discontinuation for 1-3 years. Mood stabilizers were continued in both groups. RESULTS The primary outcome was mean change on the depressive subscale of the STEP-BD Clinical Monitoring Form. Antidepressant continuation trended toward less severe depressive symptoms (mean difference in DSM-IV depression criteria = -1.84 [95% CI, -0.08 to 3.77]) and mildly delayed depressive episode relapse (HR = 2.13 [1.00-4.56]), without increased manic symptoms (mean difference in DSM-IV mania criteria = +0.23 [-0.73 to 1.20]). No benefits in prevalence or severity of new depressive or manic episodes, or overall time in remission, occurred. Type II bipolar disorder did not predict enhanced antidepressant response, but rapid-cycling course predicted 3 times more depressive episodes with antidepressant continuation (rapid cycling = 1.29 vs non-rapid cycling = 0.42 episodes/year, P = .04). CONCLUSIONS This first randomized discontinuation study with modern antidepressants showed no statistically significant symptomatic benefit with those agents in the long-term treatment of bipolar disorder, along with neither robust depressive episode prevention benefit nor enhanced remission rates. Trends toward mild benefits, however, were found in subjects who continued antidepressants. This study also found, similar to studies of tricyclic antidepressants, that rapid-cycling patients had worsened outcomes with modern antidepressant continuation. TRIAL REGISTRATION clinicaltrials.gov Identifier: NCT00012558.

Lack of Insight in Psychotic and Affective Disorders: A Review of Empirical Studies

&NA; In patients with psychotic or affective disorders, lack of insight is often a vexing clinical problem. However, it has infrequently been subjected to formal study. We have reviewed clinical psychiatric studies on insight in psychotic and affective disorders, selecting those that evaluated insight for each patient and presented the data in some quantitative fashion. Almost all studies focused on schizophrenia, with little research present on affective disorders. Definitions of insight varied among studies, as did diagnostic methods and other measures. Despite these limitations, several conclusions emerged. First, insight is not a unitary entity but has several dimensions, such as insight into symptoms and insight into need for treatment. Second, although insight may be poorer In patients with more‐severe psychopathology, it does not always improve when psychopathological symptoms do. Third, insight is associated with medication compliance, prognosis, voluntary versus involuntary admission, and cultural concepts of disease. Fourth, insight into illness, need for treatment, or delusions may respond to cognitive and psychoeducational methods of treatment. To augment these findings, we suggest further avenues of research on insight.

Diagnostic validity of comorbid bipolar disorder and obsessive–compulsive disorder: a systematic review

At least 50% of bipolar disorder (BD) patients have an additional diagnosis, one of the most difficult to manage being obsessive–compulsive disorder (OCD). Defining the nosology of BD‐OCD comorbidity has important clinical implications, given that treatments for OCD can worsen BD outcomes.

Bipolar or borderline: a clinical overview

To examine the empirical literature on diagnostic validators in borderline personality and bipolar illness.

The mistaken claim of bipolar 'overdiagnosis': solving the false positives problem for DSM-5/ICD-11.

Phelps J, Ghaemi SN. The mistaken claim of bipolar ‘overdiagnosis’: solving the false positives problem for DSM‐5/ICD‐11.

The prevalence and predictors of comorbid bipolar disorder and obsessive-compulsive disorder: A systematic review and meta-analysis

BACKGROUND Although some authors have recently investigated the co-occurrence of anxiety and bipolar disorders, the topic remains insufficiently studied. Defining the prevalence and predictors of BD-OCD comorbidity has important nosological, clinical and therapeutic implications. METHODS A systematic review and meta-analysis was conducted on the prevalence and predictors of comorbid BD-OCD. Relevant papers published through March 30th, 2015 were identified searching the electronic databases MEDLINE, Embase, PsycINFO and the Cochrane Library. RESULTS 46 articles met inclusion criteria. The pooled prevalence of OCD in BD was 17.0% (95% CI 12.7-22.4%), which was comparable to the results reported by the pooled prevalence of BD in OCD (18.35%, 95% CI 13.2-24.8%). With regard to OCD-BD predictors, a higher mean age predicted a lower prevalence of OCD in BD patients. Sub group meta-analyses reported higher OCD prevalence rates in BD children and adolescents (24.2%, compared to 13.5% in adults), in BD-I patients (24.6%, compared to 13.6% in mixed BD patients), and among population-based studies (22.2%, compared to 13.2% in hospital-based studies). LIMITATIONS Most studies use retrospective assessment scales with low sensitivity in discriminating true ego-dystonic obsessions from depressive ruminations that may bias results towards an overestimation of obsessive symptom prevalence. CONCLUSIONS This first systematic review and meta-analysis of the prevalence and predictors of comorbid BD-OCD confirms that BD-OCD comorbidity is a common condition in psychiatry with children and adolescents and BD-I patients as the most affected subgroups.

Treatment of comorbid bipolar disorder and obsessive–compulsive disorder: A systematic review

BACKGROUND More than 20% of patients with bipolar disorder (BD) show lifetime comorbidity for obsessive-compulsive disorder (OCD), but treatment of BD-OCD is a clinical challenge. Although serotonin reuptake inhibitors (SRIs) are the first line treatment for OCD, they can induce mood instability in BD. An optimal treatment approach remains to be defined. METHODS We systematically reviewed MEDLINE, Embase, PsychINFO and the Cochrane Library and retrieved data on clinical management of comorbid BD-OCD patients. Pharmacologic, psychotherapeutic and others alternative approaches were included. RESULTS Fourteen studies were selected. In all selected studies BD-OCD patients received mood stabilizers. In the largest study, 42.1% of comorbid patients required a combination of multiple mood stabilizers and 10.5% a combination of mood stabilizers with atypical antipsychotics. Addition of antidepressants to mood stabilizers led to clinical remission of both conditions in only one study. Some BD-OCD patients on mood stabilizer therapy benefitted from adjunctive psychotherapy. LIMITATIONS Most studies are case reports or cross-sectional studies based on retrospective assessments. Enrollment of subjects mainly from outpatient specialty units might have introduced selection bias and limited community-wide generalizability. CONCLUSIONS Keeping in mind scantiness and heterogeneity of the available literature, the best interpretation of the available evidence appears to be that mood stabilization should be the primary goal in treating BD-OCD patients. Addition of SRI agents seems unnecessary in most cases, although it may be needed in a minority of BD patients with refractory OCD.

DSM‐5 and the miracle that never happens

The history of psychiatry is replete with the expectation of being on the cusp of scientific breakthroughs (1). Miracles are always around the corner. Occasionally, they even happen: lithium, antipsychotics, antidepressants were all developed by pharmaceutical companies and/or solitary psychiatric researchers; the mechanisms of those agents were discovered by academic basic scientists; psychoanalysis was discovered by a Viennese private practitioner. It may be doubted whether DSM-III and IV ever led to any major discovery in psychiatry. Despite obvious advances within psychopharmacology (2), genetics (3), and neuroimaging (4), these fields have not produced impactful (i.e., replicated, large effect size) achievements in relation to psychiatric diagnoses, using DSM definitions for their clinical phenotypes, over the last three decades (5–7). This stagnation in psychiatry since the introduction of DSM-III may not be mere coincidence. We tend to blame the brain: the brain is complex, it is said, hence our decades of failed nosological genetics and imaging and pharmacology studies. Perhaps we should blame ourselves: Why should Nature order its genetics and pathophysiology and pharmacology along the lines of what the interest groups of the American Psychiatric Association may wish? Could it be that the DSM-III and IV revisions (as well as ICD-10) hindered, rather than aided, scientific progress? If so, one might rightly wonder, with DSM-5 and similarly ICD-11, whether our future can be any different than our past. Readers will forbear some explanation: There are always and only two parties in the universe, said Ralph Waldo Emerson: the party of the past and the party of the future; the Establishment and the Movement (8). There is no doubt that DSM-5 (and IV and III) is the Establishment; there is also no doubt it represents the past of psychiatry, since 1980, when DSM-III was born. The question is whether DSM-5 has a future, and whether there is any Movement in psychiatry that will promote progress for the profession. Doctor Gordon Parker makes an extensive critique of the scientific rationale for DSM-5’s various judgments on mood illnesses (9). Doctor Jan Fawcett, chairman of the DSM-5 Mood Disorders Task Force, graciously provides commentary on Doctor Parker’s essay (10). The most important aspect of Doctor Fawcett’s commentary, in my view, is his frank and honest acknowledgement that the party of the future is not going to be found in DSM-5 or its predecessors:

Borderline versus bipolar: differences matter

If you want to distinguish between two conditions, look for their differences, not their similarities. This is a simple idea, ignored by combatants in the bipolar-borderline wars. Let’s begin with mistaken similarities. The most common mistake is to see ‘mood swings’, or mood lability, as central to both conditions. ‘Mood’ is not central to mood disorders. During mania, one can be sad, happy, irritable, or anxious. The core psychopathology of bipolar illness appears to be psychomotor activation (1). In contrast, most patients with borderline personality do not have such psychomotor activation (decreased need for sleep with increased energy, increased goal-directed activities, pressured speech) – especially episodically. Some claim that impulsivity is central to both conditions. But most manic, and all hypomanic, episodes, do not involve notable impulsive behavior [the minority of manic episodes involve sexual indiscretions or impulsive spending (2)]. Similarly, although borderline personality can have mood lability, this feature is variable; borderline patients sometimes are impulsive in behavior, but they are not always so. This clinical debate about overlap is scientifically false. The ‘core’ features of mood lability and impulsivity are not central to either illness. The concept of mood temperaments further complicates matters. Bipolar illness is episodic, whereas personality disorders are constant. This is one key distinction. But mood temperaments, like cyclothymia or hyperthymia (constant mild manic features), are also constant (3). If mood lability is seen as central, little distinction exists on that feature between cyclothymic or hyperthymic temperaments vs. borderline personality. Let’s turn to the useful differences between these conditions. Self-destructive cutting behavior is highly uncommon in bipolar illness, but common in borderline personality (50–80%). Bipolar disorder is almost completely genetic, about 80–90% heritable, similar to physical height (4). Borderline personality is much less genetic, with about half the genetic loading, similar to anxiety conditions. If bipolar illness is present in the family, based on the above data, then bipolar illness is highly probable in a proband. Finally, borderline personality is highly associated with sexual trauma (40–70%); the prevalence of sexual trauma in bipolar illness (20–40%), although higher than the general population (13–17% in women and 2.5 –5% in men), is half that in borderline personality. These differences help us better appreciate this analysis from the BRIDGE study. The BRIDGE data are reported mostly in terms of overlap between these two conditions. What matters more is how they differ. In terms of overlap, 4/9 borderline criteria predicted bipolar illness. Critics might cite the inherent overlap of mood lability in the broad bipolarity specifier definition of the BRIDGE study, but this broad definition does not mean that those patients have borderline personality either, because mood lability is neither central nor specific to borderline personality, happening also in bipolar illness and other conditions. The more striking finding is that four borderline features were not predictive of bipolarity even using the broad bipolarity specifier: abandonment, identity disturbance, recurrent suicidal or self-mutilating behavior, and dissociative symptoms. These borderline features are all the more impressive when one appreciates that this is a sample of patients with clinical depression in which the prior probability of bipolar illness, simply based on presence of depression and the clinical/demographic features of the sample, is about 50%. As DSM ignores possible causes, and childhood sexual abuse is not listed among DSM criteria, these data do not assess that important predictor of borderline personality. We think it likely would differ as well. In sum, these data are quite useful, if viewed from the perspective of how these conditions differ, not how they appear similar. Look for the differences: if patients have sexual trauma and/or self-mutilation and/or dissociation, borderline personality is probable and bipolar illness unlikely. If patients have a family history of bipolar illness and marked episodic psychomotor activation, in the absence of sexual trauma and selfmutilation, it would seem indefensible to diagnose borderline personality. Still, there will be differences of opinion, which leads us to offer a final comment. Unfortunately, it is a truism of sociology that political and economic factors influence professional debates. One proponent of borderline personality has even decried ‘bipolar imperialism’ (5), as if certain ‘territory’ is being invaded by a foreign group. Such rhetoric can easily be turned around: it can be claimed that borderline ‘imperialism’ led to marked bipolar underdiagnosis from the 1960s through the 1990s, and even today. Furthermore, manic depression has been described in the scientific literature for almost two centuries, with literally thousands of nosologic validity studies (symptoms, genetics, course, treatment effects, and biology); borderline personality, in contrast, is a psychoanalytic construct of about 50 years vintage, with a few dozen, at most, studies of nosologic validity. These are not nosologic equals: A clearly valid disease is being compared with a psychological construct. In that comparison, instead of political rhetoric, this kind of scientific research can help clarify the controversy.