Antidepressants in bipolar disorder: the case for caution

Ghaemi, S. Nassir; Hsu, Douglas J.; Soldani, Federico; Goodwin, Frederick K.

doi:10.1046/j.1399-5618.2003.00074.x

Cited by 309 publications

(201 citation statements)

References 69 publications

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“…[72][73][74] Furthermore, drugs or conditions known to induce mania in susceptible individuals 171 could be studied using 11 C-labeled AA and PET. Because antidepressants can induce switching to mania when given to a depressed bipolar disorder patient, 146,[172][173][174] we examined the selective serotonin reuptake inhibitor fluoxetine in our models. Opposite to the antimanic drugs, chronic fluoxetine increased frontal cortex cPLA 2 activity, protein and mRNA expression along with the turnover of AA in brain phospholipids of the unanesthetized rat.…”

Section: Observations Related To Aa In Bipolar Disorder Patientsmentioning

confidence: 99%

Mode of action of mood stabilizers: is the arachidonic acid cascade a common target?

et al. 2008

Mol Psychiatry

108

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Bipolar disorder is a major medical, social and economic burden worldwide. However, the mechanisms of action of effective antibipolar disorder drugs remain elusive. In this paper, we review studies using a neuropharmacological approach in unanesthetized rats, combined with kinetic, biochemical and molecular biology techniques, showing that chronic administration of three Food and Drug Administration-approved mood stabilizers (lithium, valproate and carbamazepine) at therapeutically relevant doses, selectively target the brain arachidonic acid (AA) cascade. Whereas chronic lithium and carbamazepine decrease the binding activity of activator protein-2 and in turn the transcription, translation and activity of its AA-selective calcium-dependent phospholipase A 2 gene product, valproate appears to be a non-competitive inhibitor of long-chain acyl-CoA synthetase. The net overlapping effects of the three drugs are decreased turnover of AA but not of docosahexaenoic acid in rat brain phospholipids, and decreased brain cyclooxygenase-2 and prostaglandin E 2 . Although these observations support the hypothesis proposed by Rapoport and colleagues that the AA cascade is a common target of mood stabilizers, this hypothesis is not necessarily exclusive of other targets. Targeting the AA cascade with drugs or diet may be a useful therapeutic approach in bipolar disorder, and examining the AA cascade in patients might help in better understanding the disease.

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Section: Observations Related To Aa In Bipolar Disorder Patientsmentioning

confidence: 99%

Mode of action of mood stabilizers: is the arachidonic acid cascade a common target?

et al. 2008

Mol Psychiatry

108

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“…One group of experts focus on: (1) the potential negative consequences of antidepressants -the risk of pharmacological manias/hypomanias and mood destabilization; (2) the greater database on lithium's efficacy in preventing suicide compared to antidepressants; (3) the lack of consistent efficacy of antidepressants in both acute bipolar depression and their lesser efficacy compared to mood stabilizers in preventing depression; and (4) the efficacy of lithium and lamotrigine for both acute bipolar depression and as maintenance treatments. 104 In contrast, others examine the same database and conclude that the database for efficacy of mood stabilizers in treating bipolar depression is weak, the efficacy of antidepressants greater and the switch rate associated with the newer antidepressants substantially lower than for the first-generation agents (tricyclics and monoamine oxidase inhibitors). 101,105 In general, however, we can assume that lithum, lamotrigine, OFC and antidepressants (combined with mood stabilizers) comprise first-line treatments for bipolar I depression.…”

Section: First-line Treatment Of Bipolar Depressionmentioning

confidence: 99%

Treatment-resistant bipolar disorder

2006

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Despite the remarkable increase in medications validated as effective in bipolar disorder, treatment is still plagued by inadequate response in acute manic or depressive episodes or in long-term preventive maintenance treatment. Established first-line treatments include lithium, valproate and second-generation antipsychotics (SGAs) in acute mania, and lithium and valproate as maintenance treatments. Recently validated treatments include extended release carbamazapine for acute mania and lamotrigine, olanzapine and aripiprazole as maintenance treatments. For treatment-resistant mania and as maintenance treatments, a number of newer anticonvulsants, and one older one, phenytoin, have shown some promise as effective. However, not all anticonvulsants are effective and each agent needs to be evaluated individually. Combining multiple agents is the most commonly used clinical strategy for treatment resistant bipolar patients despite a relative lack of data supporting its use, except for acute mania (for which lithium or valproate plus an SGA is optimal treatment). Other approaches that may be effective for treatment-resistant patients include high-dose thyroid augmentation, clozapine, calcium channel blockers and electroconvulsive therapy (ECT). Adjunctive psychotherapies show convincing efficacy using a variety of different techniques, most of which include substantial attention to education and enhancing coping strategies. Only recently, bipolar depression has become a topic of serious inquiry with the dominant controversy focusing on the place of antidepressants in the treatment of bipolar depression. Other than mood stabilizers alone or the combination of mood stabilizers and antidepressants, most of the approaches for treatment-resistant bipolar depression are relatively similar to those used in unipolar depression, with the possible exception of a more prominent place for SGAs, prescribed either alone or in combination with antidepressants. Future work in the area needs to explore the treatments commonly used by clinicians with inadequate research support, such as combination therapy and the use of antidepressants as both acute and adjunctive maintenance treatments for bipolar disorder. With the first report of lithium's efficacy in 1949 by Cade, bipolar disorder has the longest record of treatment efficacy among the major Axis I disorders. Furthermore, after more than half a century of clinical research, multiple agents from many different pharmacological classes have shown at least some efficacy, while many other agents (albeit without a consistent database demonstrating their utility) are prescribed regularly by clinicians. Yet, despite this plethora of choices, treatment of bipolar disorder remains suboptimal from the points of view of clinicians and patients alike. Whether measured by recovery time from manic or depressive episodes or preventive efficacy of maintenance treatments, bipolar disorder is characterized by sluggish responses, inadequate responses, poor compliance and recurrences in controlled cli...

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“…This phase of bipolar illness is of particular significance in that it is associated with substance abuse, disability, and premature mortality due to suicide or medical illnesses (Tondo et al, 2003a;Carney & Jones, 2006;Newcomer, 2006). Moreover, it remains the least well studied type of depressive illness, for which very few treatments are proved safe and effective (Ghaemi et al, 2003;2004;Baldessarini, 2005;Goodnick, 2007).…”

Section: Early Morbidity During Follow-up Of Bipolar Disorder Patientsmentioning

confidence: 99%

Longitudinal research on bipolar disorders

Salvatore¹,

Tohen²,

Khalsa³

et al. 2007

Epidemiol Psichiatr Soc

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Abstract. Longitudinal assessment of the course of major psychiatric disorders has been advanced by studies from onset, but only rarely have large numbers of patients with a range of psychotic and major affective disorders been studied simultaneously and systematically from illness-onset. The decade-long McLean-Harvard First Episode Project & International Consortium for Bipolar Disorder Research has systematically followed-up large numbers of patients with DSM-IV bipolar or psychotic disorders from firsthospitalization. Major findings among patients with bipolar I disorder include: [a] full functional recovery from initial episodes was uncommon, and full symptomatic recovery, much slower than early syndromal recovery; [b] risks of relapse, recurrence, and switching were very high in the first two years; [c] most early morbidity was depressive-dysphoric, as reported in mid-course; [d] initial depression or mixed-states predicted more later depressive and overall morbidity, whereas initial mania or psychosis predicted later mania and a better prognosis; [e] based on within-subject modeling, most patients did not show progressive cycling over time, and illness-course was rather chaotic within and among patients; [f] treatment-latency or episode-counts were unassociated with responsiveness to long-term mood-stabilizing treatment; [g] very high rates of suicidal behavior and accidents occurred early; [h] early substance-use comorbidity associated with anxiety; [i] factor-analysis of prodromal symptoms predicted bipolar disorder much better than non-affective psychotic disorders. Project findings indicate that the course of bipolar I disorder is much less favorable than had been believed formerly, despite clinical treatment with modern mood-stabilizing and other treatments.

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Antidepressants in bipolar disorder: the case for caution

Cited by 309 publications

References 69 publications

Mode of action of mood stabilizers: is the arachidonic acid cascade a common target?

Mode of action of mood stabilizers: is the arachidonic acid cascade a common target?

Treatment-resistant bipolar disorder

Longitudinal research on bipolar disorders

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