When and how to use lithium.

BACKGROUND: Lithium is an old proven medication, but it is infrequently used in current practice. This review examines evidence for its benefits and risks and provides clinical guidance to its use. METHOD: Narrative review. RESULTS: Besides its benefit in bipolar illness, lithium has important underappreciated proven benefits in prevention of unipolar depression and suicide. Emerging data support neurobiological benefits for cognition and possible dementia prevention. Likely benefits also exist in low doses for mood temperaments (cyclothymia and hyperthymia). High doses (over 1.0 mmol/L) should be avoided since they increase side effects, complications associated with long-term use, and risk of toxicity. Conversely, low dosing can be legitimate, especially for suicide and dementia prevention. Nuisance side effects of lithium may affect adherence, and medically serious side-effects can occur. Managing strategies are available for side effects. CONCLUSION: Lithium is the most effective medication in psychiatry, because it has disease-modifying, not just symptomatic, effects. It is effective not only for bipolar illness but also for prevention of suicide, episodes of unipolar depression, mood temperaments, and possibly dementia. Its many benefits need better appreciation, while lowered dosing can reduce risks.

Digital depression: a new disease of the millennium?

OBJECTIVE: In the past decade, since the innovation of the smartphone, there has been an increase in depression, anxiety, and suicidality among teenagers and young adults. The objective of this article was to review the current evidence for these associations and to provide initial clinical guidance. METHODS: A narrative review of the available literature on digital technology, social media, and psychiatric outcomes in adolescents. RESULTS: Psychiatric outcomes have worsened in adolescents in the past decade, correlating with the invention of the smartphone and the rise of social media. Depressive symptoms among American teenagers rose rapidly around 2012 and now are reported in 22% of adolescents, which is at least double the rate in adults. Suicide rates have risen, especially among teenage girls in the United States, in whom there has been a doubling of completed suicide in the past decade. A causal relationship between social media use and these harmful psychiatric outcomes is supported by emerging randomized data showing reduced depressive symptoms associated with a decrease in social media use in college students. CONCLUSIONS: Social media and digital technology correlate with harmful psychiatric outcomes in adolescents and young adults. Clinical recommendations should include limitations in social media use.

Updates in treating comorbid bipolar disorder and obsessive-compulsive disorder: A systematic review.

BACKGROUND: In the last five years, the debate around the comorbidity between bipolar disorder (BD) and obsessive-compulsive disorder (OCD) has flourished within the international psychiatric community and several studies have been published on therapeutic strategies. METHODS: An update of our previous systematic review was conducted on clinical management of comorbid BD-OCD patients. Relevant papers published from July 1st 2013 to September 30th 2018 were identified searching the electronic databases MEDLINE, Embase, PsycINFO and the Cochrane Library. RESULTS: Fifteen studies were included. In all selected studies BD-OCD patients received mood stabilizers, alone or with second-generation antipsychotics (SGAs). Aripiprazole augmentation demonstrated to be effective as maintenance therapy and for treating obsessive-compulsive symptoms during manic episodes (40% of the studies, 6/15). Addition of antidepressants to mood stabilizers led to clinical remission of both conditions in only one case report. LIMITATIONS: Almost 50% of the selected studies are case reports. Enrolment of subjects mainly from outpatient specialty units might have introduced selection bias and limited community-wide generalizability. CONCLUSIONS: Mood stabilization should be the primary goal in treating BD-OCD patients. Aripiprazole augmentation to lithium carbonate seemed to be the best option in treatment-resistance comorbid patients. Addition of SRIs may be needed only in a minority of BD patients with refractory OCD.

Aripiprazole augmentation in treating comorbid bipolar disorder and obsessive-compulsive disorder: A systematic review.

BACKGROUND: Apparent comorbidity between bipolar disorder (BD) and obsessive-compulsive disorder (OCD) is a common condition in psychiatry, but treatment of BD-OCD remains 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: A systematic review was conducted on aripiprazole augmentation in treating comorbid BD-OCD patients. Relevant papers published through August 31st 2018 were identified searching the electronic databases MEDLINE, Embase, PsycINFO and the Cochrane Library. RESULTS: Aripiprazole augmentation to mood stabilizers (lithium carbonate, valproate), even at low doses (10-15 mg/day), helped to achieve significant remission in affective and obsessive-compulsive symptoms. Aripiprazole was generally safe and well tolerated. LIMITATIONS: Most studies are case reports. Enrolment 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 aripiprazole augmentation to mood stabilizers, even at low doses, is effective in BD-OCD patients.

Safety and efficacy of lithium in children and adolescents: A systematic review in bipolar illness.

INTRODUCTION: Many clinicians are reluctant to use traditional mood-stabilizing agents, especially lithium, in children and adolescents. This review examined the evidence for lithium's safety and efficacy in this population. METHODS: A systematic review was conducted on the use of lithium in children and adolescents with bipolar disorder (BD). Relevant papers published through June 30th 2018 were identified searching the electronic databases MEDLINE, Embase, PsycINFO and the Cochrane Library. RESULTS: 30 articles met inclusion criteria, including 12 randomized controlled trials (RCTs). Findings from RCTs demonstrate efficacy for acute mania in up to 50% of patients, and evidence of long-term maintenance efficacy. Lithium was generally safe, at least in the short term, with most common side effects being gastrointestinal, polyuria, or headache. Only a minority of patients experienced hypothyroidism. No cases of acute kidney injury or chronic kidney disease were reported. CONCLUSIONS: Though the available literature is mostly short-term, there is evidence that lithium monotherapy is reasonably safe and effective in children and adolescents, specifically for acute mania and for prevention of mood episodes.

Maintenance efficacy designs in psychiatry: Randomized discontinuation trials - enriched but not better.

INTRODUCTION: Although classical randomized clinical trials (RCTs) are the gold standard for proof of drug efficacy, randomized discontinuation trials (RDTs), sometimes called "enriched" trials, are used increasingly, especially in psychiatric maintenance studies. METHODS: A narrative review of two decades of experience with RDTs. RESULTS: RDTs in psychiatric maintenance trials tend to use a dependent variable as a predictor: treatment response. Treatment responders are assessed for treatment response. This tautology in the logic of RDTs renders them invalid, since the predictor and the outcome are the same variable. Although RDTs can be designed to avoid this tautologous state of affairs, like using independent predictors of outcomes, such is not the case with psychiatric maintenance studies Further, purported benefits of RDTs regarding feasibility were found to be questionable. Specifically, RDTs do not enhance statistical power in many settings, and, because of high dropout rates, produce results of questionable validity. Any claimed benefits come with notably reduced generalizability. CONCLUSIONS: RDTs appear to be scientifically invalid as used in psychiatric maintenance designs. Their purported feasibility benefits are not seen in actual trials for psychotropic drugs. There is warrant for changes in federal policy regarding marketing indications for maintenance efficacy using the RDT design.

The International Mood Network (IMN) Nosology Project: differentiating borderline personality from bipolar illness.

OBJECTIVE: The differential diagnosis of bipolar illness vs. borderline personality is controversial. Both conditions manifest impulsive behavior, unstable interpersonal relationships, and mood symptoms. This study examines whether and which mood clinical features can differentiate between both conditions. METHOD: A total of 260 patients (mean ± standard deviation age 41 ± 13 years, 68% female) attending to a mood clinic were examined for diagnosis of bipolar illness and borderline personality disorder using SCID-I, SCID-II, and clinical mood criteria extracted from Mood Disorder Questionnaire (MDQ). They were analyzed using diagnoses as dependent variables. Predictors of bipolar and borderline diagnoses were identified by multivariable logistic regressions, and predictive validity of models was assessed using ROC curve analysis. RESULTS: Bipolar illness was strongly predicted by elevated mood (OR = 4.02, 95% CI: 1.80-9.15), increased goal-directed activities (OR = 3.90, 95% CI: 1.73-8.96), and episodicity of mood symptoms (OR = 3.48, 95% CI 1.49-8.39). This triad model predicted bipolar illness with 88.7% sensitivity, 81.4% specificity, and obtained an auROC of 0.91 (95% CI: 0.76-0.96) and a positive predictive value of 85.1%. For borderline personality disorder, only female gender was a statistically significant predictor (OR = 3.41, 95% CI: 1.29-13.7), and the predictive model obtained an auROC of 0.67 (95% CI: 0.53-0.74). CONCLUSION: In a mood disorder clinic setting, manic criteria and episodic mood course distinguished bipolar illness from borderline personality disorder.

Course of illness in comorbid bipolar disorder and obsessive-compulsive disorder patients.

Psychiatric comorbidity is extremely common. One of the most common and difficult to manage comorbid conditions is the co-occurrence of bipolar disorder (BD) and obsessive compulsive disorder (OCD). We updated our recent systematic review searching the electronic databases MEDLINE, Embase, and PsycINFO to investigate course of illness in BD-OCD patients. We identified a total of 13 relevant papers which found that the majority of comorbid OCD cases appeared to be related to mood episodes. OC symptoms in comorbid patients appeared more often during depressive episodes, and comorbid BD and OCD cycled together, with OC symptoms often remitting during manic/hypomanic episodes.

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.