Comorbidity of depressive and anxiety disorders is common and remains incompletely comprehended. This paper summarizes findings from the Netherlands Study of Depression and Anxiety (NESDA) regarding prevalence, temporal sequence, course and longitudinal patterns; sociodemographic, vulnerability and neurobiological indicators; and functional, somatic and mental health indicators of comorbidity. Narrative synthesis of earlier NESDA based papers on comorbidity (n=76). Comorbidity was the rule in over three-quarter of subjects with depressive and/or anxiety disorders, most often preceded by an anxiety disorder. Higher severity and chronicity characterized a poorer comorbidity course. Over time, transitions between depressive and anxiety disorders were common. Consistent comorbidity risk indicators in subjects with depressive and anxiety disorders were childhood trauma, neuroticism and early age of onset. Psychological vulnerabilities, such as trait avoidance tendencies, were more pronounced in comorbid than in single disorders. In general, there were few differences in biological markers and neuroimaging findings between persons with comorbid versus single disorders. Most functional, somatic, and other mental health indicators, ranging from disability to cardiovascular and psychiatric multimorbidity, were highest in comorbid disorders. The observational design of NESDA limits causal inference. Attrition was higher in comorbid relative to single disorders. As compared to single disorders, persons with comorbid depressive and anxiety disorders were characterized by more psychosocial risk determinants, more somatic and other psychiatric morbidities, more functional impairments, and poorer outcome. These results justify specific attention for comorbidity of depressive and anxiety disorders, particularly in treatment settings.

Rapid cycling, defined as 4 or more mood episodes per year, is a course specifier of bipolar disorder associated with relative treatment resistance. Several risk factors have been suggested to be associated with rapid cycling. The purpose of this meta-analysis was to compare clinical studies for the evidence of discriminating factors between rapid and non-rapid cycling. We searched MEDLINE and reference lists of articles and book chapters and selected all of the clinical studies published from 1974 to 2002 comparing subjects with rapid and non-rapid cycling bipolar disorder. Prevalence rates and mean random effect sizes for 18 potential risk factors that were reported by at least 3 studies were calculated. In addition, we differentiated between current and lifetime diagnoses of rapid cycling. Twenty studies were identified. Rapid cycling was present in 16.3% of 2054 bipolar patients in 8 studies that included patients who were consecutively admitted to an inpatient or outpatient facility, without a priori selection of rapid cyclers and without matching the numbers of rapid cyclers to non-rapid cycling controls. Female gender and bipolar II subtype both had a small, but statistically significant, effect (p <.000 for female gender, p <.001 for bipolar II subtype). The further absence of recurrences with lithium prophylaxis was reported in 34% of rapid cyclers compared with 47% of non-rapid cyclers, a nearly significant difference, and a partial response was present in 59% and 65% of patients, respectively. The effect of hypothyroidism was significant (p <.01) in studies using current, but not lifetime, definitions of rapid cycling. In 46% of cases, a rapid cycling course was preceded by treatment with antidepressants, but systematic data on their causal role are lacking. Rapid cycling is slightly more prevalent in women and in patients with bipolar II subtype. In contrast to common opinion, lithium prophylaxis has at least partial efficacy in a considerable number of rapid cyclers, especially when antidepressants are avoided. Hypothyroidism may be associated with mood destabilization in vulnerable patients.

Pharmacotherapy is an effective treatment modality across psychiatric disorders. Nevertheless, many patients discontinue their medication at some point. Evidence-based guidance for patients, clinicians, and policymakers on rational discontinuation strategies is vital to enable the best, personalized treatment for any given patient. Nonetheless, there is a scarcity of guidelines on discontinuation strategies. In this perspective, we therefore summarize and critically appraise the evidence on discontinuation of six major psychotropic medication classes: antidepressants, antipsychotics, benzodiazepines, mood stabilizers, opioids, and stimulants. For each medication class, a wide range of topics pertaining to each of the following questions are discussed: (1) Who can discontinue (e.g., what are risk factors for relapse?); (2) When to discontinue (e.g., after 1 year or several years of antidepressant use?); and (3) How to discontinue (e.g., what’s the efficacy of dose reduction compared to full cessation and interventions to mitigate relapse risk?). We thus highlight how comparing the evidence across medication classes can identify knowledge gaps, which may pave the way for more integrated research on discontinuation.

Objectives: Clinical staging is widely used in medicine to map disease progression, inform prognosis, and guide treatment decisions; in psychiatry, however, staging remains a hypothetical construct. To facilitate future research in bipolar disorders (BD), a well‐defined nomenclature is needed, especially since diagnosis is often imprecise with blurred boundaries, and a full understanding of pathophysiology is lacking.Methods: Under the auspices of the International Society of Bipolar Disorders, a Task Force of international experts was convened to review, discuss, and integrate findings from the scientific literature relevant to the development of a consensus staging model and standardize a terminology that could be used to advance future research including staging of BD and related disorders.Results: Consensus opinion and areas of uncertainty or difference were identified in regard to terms referring to staging as it may apply to BD, to at‐risk status and subthreshold stages, and to various clinical stages of BD as it is currently diagnosed.Conclusion: The use of a standardized nomenclature about the clinical stages of BD will facilitate communication about research on clinical and pathological components of this heterogeneous group of disorders. The concepts presented are based on current evidence, but the template provided allows for further refinements as etiological advances come to light.