Bipolar depression: a major unsolved challenge

Abstract

Depression in bipolar disorder (BD) patients presents major clinical challenges. As the predominant psychopathology even in treated BD, depression is associated not only with excess morbidity, but also mortality from co-occurring general-medical disorders and high suicide risk. In BD, risks for medical disorders including diabetes or metabolic syndrome, and cardiovascular disorders, and associated mortality rates are several-times above those for the general population or with other psychiatric disorders. The SMR for suicide with BD reaches 20-times above general-population rates, and exceeds rates with other major psychiatric disorders. In BD, suicide is strongly associated with mixed (agitated-dysphoric) and depressive phases, time depressed, and hospitalization. Lithium may reduce suicide risk in BD; clozapine and ketamine require further testing. Treatment of bipolar depression is far less well investigated than unipolar depression, particularly for long-term prophylaxis. Short-term efficacy of antidepressants for bipolar depression remains controversial and they risk clinical worsening, especially in mixed states and with rapid-cycling. Evidence of efficacy of lithium and anticonvulsants for bipolar depression is very limited; lamotrigine has long-term benefit, but valproate and carbamazepine are inadequately tested and carry high teratogenic risks. Evidence is emerging of short-term efficacy of several modern antipsychotics (including cariprazine, lurasidone, olanzapine-fluoxetine, and quetiapine) for bipolar depression, including with mixed features, though they risk adverse metabolic and neurological effects.

Long‐term morbidity in major affective and schizoaffective disorders following hospitalization in first psychotic episodes

“…Particularly notably, however, all subjects spent relatively large proportions of time in dysthymic (subsyndromal depressive) states: MDD (24.0%) ≥ SzAffD (21.4%) ≥ BD‐I (16.5%), as well as in the total of major depression and dysthymia: MDD (54.5%) > SzAffD (30.7%) > BD‐I (17.2%; Table ). These findings reflect the ongoing challenge of successful long‐term treatment of depression and dysthymia in major mood disorder and schizoaffective disorder patients, with associated disability and suicidal risks 35–37 …”

General medical conditions and mortality in women with postpartum psychiatric disorders

“…Research in previous years has documented patients with severe psychiatric disorders, in general, have an alarmingly increased risk of subsequent chronic medical conditions and premature death (1)(2)(3)(4)(5)(6). This excess mortality stems partly from an elevated risk of unnatural deaths, including accidents, suicides, and homicides.…”

MNAD Hypothesis Based Protocol Proposed for Treatment of COVID.19: Assessment of Minocycline, N. acetylcysteine, Aspirin & vitamin D (MNad) Theory for treatment of COVID.19 Adults Patients

“…With BD, risk of myocardial infarction was 37% greater, stroke 60%, and congestive heart failure nearly 230% greater than in age-matched general populations. Mediating factors include obesity, inactivity, diabetes or metabolic syndrome, and increased inflammatory factors-all with increased prevalence among BD patients [7]. Bipolar disorder in youth associated with increased levels of vitamin D-binding protein [8] and that means low levels of vitamin D. Also increased risk for pulmonary embolism in patients with bipolar disorder was observed [9].…”