Pharmacological treatment of adult bipolar disorder

Baldessarini, Ross J.; Tondo, Leonardo; Vázquez, Gustavo

doi:10.1038/s41380-018-0044-2

Cited by 156 publications

(142 citation statements)

References 149 publications

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“…In mood-disorder patients depressive-dysphoric phases are more associated with suicide than other illness states, especially if accompanied by mixed (hypomanic) features, co-occurring substance abuse, and following previous suicidal acts (Tondo et al 1999Baldessarini et al 2019b). General population rates of suicide attempts average 0.2-0.6% per year, or approximately 36-times the suicide rate, and over 1%/year in BD (Kessler et al 2005;Nock et al 2008;Tondo et al 2016;Baldessarini et al 2019b). The ratio of suicide attempts/suicides (A/S), an index of lethality lower with more lethal intent or method, is only 5-10 in BD and MDD, or about fivetimes above lower than that for the general population (Tondo and Baldessarini 2015;Baldessarini et al 2019b).…”

Section: Suicidal Risksmentioning

confidence: 99%

“…General population rates of suicide attempts average 0.2-0.6% per year, or approximately 36-times the suicide rate, and over 1%/year in BD (Kessler et al 2005;Nock et al 2008;Tondo et al 2016;Baldessarini et al 2019b). The ratio of suicide attempts/suicides (A/S), an index of lethality lower with more lethal intent or method, is only 5-10 in BD and MDD, or about fivetimes above lower than that for the general population (Tondo and Baldessarini 2015;Baldessarini et al 2019b).…”

Section: Suicidal Risksmentioning

confidence: 99%

“…Among both BD-I and BD-II patients, especially with mixed or psychotic features, risk of suicidal behavior is among the highest of all psychiatric disorders despite supposedly effective treatments (Baldessarini et al 2019b). This disparity almost certainly reflects great difficulty of treating depressive and mixed states in BD (Baldessarini et al 2010c;Saunders and Hawton 2013;Forte et al 2015).…”

Section: Suicidal Risksmentioning

confidence: 99%

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Bipolar depression: a major unsolved challenge

Baldessarini

Vázquez

Tondo

2020

Int J Bipolar Disord

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137

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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.

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Section: Suicidal Risksmentioning

confidence: 99%

Section: Suicidal Risksmentioning

confidence: 99%

Section: Suicidal Risksmentioning

confidence: 99%

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Bipolar depression: a major unsolved challenge

Baldessarini

Vázquez

Tondo

2020

Int J Bipolar Disord

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137

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“…MDD symptoms include low mood, anhedonia, decreased energy, altered appetite, weight loss, irritability, sleep disturbances, and cognitive deficits. 6,7 Therefore, there is an urgent requisite for additional effective therapeutic options for the treatment of MDD. [2][3][4] The first line pharmacotherapy for MDD include selective serotonin reuptake inhibitors (SSRIs) with a patient response rate of approximately 30%.…”

Section: Introductionmentioning

confidence: 99%

Mitochondria could be a potential key mediator linking the intestinal microbiota to depression

Chen¹,

Vitetta

2019

J of Cellular Biochemistry

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The intestinal microbiota has been reported to affect depression, a common mental condition with severe health‐related consequences. However, what mediates the effect of the intestinal microbiota on depression has not been well elucidated. We summarize the roles of the mitochondria in eliciting beneficial effects on the gut microbiota to ameliorate symptoms of depression. It is well known that mitochondria play a key role in depression. An important pathogenic factor, namely inflammatory response, may adversely impact mitochondrial functionality to maintain cellular homeostasis. Dysfunction of mitochondria not only affects neuronal function but also reduces neuron cell numbers. We posit that the intestinal microbiota could affect neuronal mitochondrial function through short‐chain fatty acids such as butyrate. Brain inflammatory processes could also be affected through the modulation of gut permeability and blood lipopolysaccharide levels. Aberrant mitochondria functionality coupled to adverse cellular homeostasis could be a key mediator for the effect of the intestinal microbiota on the progression of depression.

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“…We also think that the authors should be careful in considering diverse pharmacological treatments (from antidepressants to mood stabilizers) deemed to be equally effective in controlling suicidality. In mood disorders, lithium is the only drug that significantly reduces suicidal risk (both ideation and acts), probably even in the absence of an effective mood stabilization . Finally, and possibly more importantly, we should all be mindful that suicide behaviour remains a very rare event.…”

mentioning

confidence: 99%

A parsimonious approach to suicide prevention in mood disorders

Manchia

Tondo

2018

Bipolar Disorders

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To the Editors, In their erudite commentary, Ballard and Zarate 1 advocate that, to be effective, suicide prevention strategies should be considerate of the multifactorial nature of this complex behaviour. Undoubtedly, prediction and prevention of suicide behaviour are very challenging tasks given its complex biological underpinnings, the uneven distribution of its risk over a lifetime trajectory, and the very different magnitude of risk associated with each determinant, either proximal or distal. However, we are less optimistic about the efficacy of the potential primary and secondary preventive options indicated by the authors, namely the Good Behaviour Game (GBG) and the glutamatergic modulator ketamine, on the basis of some phenomenological, epidemiological and pharmacological considerations. Suicide behaviour manifests according to a specific trajectory of severity (from suicide ideation to acts and eventually death by suicide). However, this trajectory might not necessarily be characterized by a temporal and hierarchical consequentiality, since suicide ideation is an almost necessary factor for suicide but rarely sufficient. Indeed, epidemiological data show that only a small proportion of patients who manifest suicide thoughts go on to commit an attempt, 2 and risk factors might be distinctly associated with suicide ideation or suicide acts. 3Of interest, the National Comorbidity Survey data showed that the risk of attempt was even higher among patients who presented suicide ideation without plan (odds ratio [OR] 2.5) than among those who had planned attempts (OR 1.5). 3 This evidence put clinicians in a quandary as to whether ketamine, a promising and plausibly effective treatment for depression and therefore possibly useful in controlling suicide ideation, might be successful in patients at high risk for suicidal acts, such as those with a personal history of previous attempts. Moreover, ketamine seems to be effective for short periods of time; thus it is hard to delineate its precise role in a therapeutic strategy for the treatment of suicide ideation. We also think that the authors should be careful in considering diverse pharmacological treatments (from antidepressants to mood stabilizers) deemed to be equally effective in controlling suicidality. In mood disorders, lithium is the only drug that significantly reduces suicidal risk (both ideation and acts), 4 probably even in the absence of an effective mood stabilization. 5 Finally, and possibly more importantly, we should all be mindful that suicide behaviour remains a very rare event. Thus, primary preventive strategies, such as GBG, although effective, would need such a large-scale and extensive implementation that their feasibility would inevitably be impacted. In summary, we agree that suicide behaviour should be considered in the light of its complexity. At the same time, we reckon that the search for complex answers to a complex problem should not lead to parsimonious solutions, such as the prevention of mood altered episodes, especially of dep...

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Pharmacological treatment of adult bipolar disorder

Cited by 156 publications

References 149 publications

Bipolar depression: a major unsolved challenge

Bipolar depression: a major unsolved challenge

Mitochondria could be a potential key mediator linking the intestinal microbiota to depression

A parsimonious approach to suicide prevention in mood disorders

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