Mood Stabilizer Combinations: A Review of Safety and Efficacy

Freeman, Marlene P.; Stoll, Andrew L.

doi:10.1176/ajp.155.1.12

Cited by 185 publications

(81 citation statements)

References 97 publications

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“…In this context, it is noteworthy that the combination of lithium and VPA reportedly causes an additive suppression of brain levels of myristoylated alanine-rich C kinase substrate, a potential molecular target of mood stabilizers (Lenox et al, 1996). Several atypical antipsychotic drugs have also been used in conjunction with lithium or VPA to maximize the clinical efficacy for bipolar disorder (for review, see Freeman and Stoll, 1998;Bachmann et al, 2005;Lin et al, 2006). It would thus be of interest to investigate whether the synergy in neuroprotection can be elicited by antipsychotic drug cotreatment with lithium/VPA.…”

Section: Discussionmentioning

confidence: 99%

“…Combined treatment with mood stabilizers has been a frequently used strategy to control bipolar syndromes resistant to monotherapy. One of the most efficacious and safe mood stabilizer combinations appears to be a mixture of lithium and anticonvulsants, notably VPA (for review, see Freeman and Stoll, 1998;Lin et al, 2006). The present study was undertaken to search for an experimental paradigm in which the neuroprotective actions of lithium and VPA or other HDAC inhibitors can be dramatically potentiated and to determine whether GSK-3 is a molecular target for the synergistic neuroprotection elicited by combined drug treatment.…”

Section: Introductionmentioning

confidence: 99%

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Synergistic Neuroprotective Effects of Lithium and Valproic Acid or Other Histone Deacetylase Inhibitors in Neurons: Roles of Glycogen Synthase Kinase-3 Inhibition

Leng

Liang²,

Ren³

et al. 2008

J. Neurosci.

198

146

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Lithium and valproic acid (VPA) are two primary drugs used to treat bipolar mood disorder and have frequently been used in combination to treat bipolar patients resistant to monotherapy with either drug. Lithium, a glycogen synthase kinase-3 (GSK-3) inhibitor, and VPA, a histone deacetylase (HDAC) inhibitor, have neuroprotective effects. The present study was undertaken to demonstrate synergistic neuroprotective effects when both drugs were coadministered. Pretreatment of aging cerebellar granule cells with lithium or VPA alone provided little or no neuroprotection against glutamate-induced cell death. However, copresence of both drugs resulted in complete blockade of glutamate excitotoxicity. Combined treatment with lithium and VPA potentiated serine phosphorylation of GSK-3 ␣ and ␤ isoforms and inhibition of GSK-3 enzyme activity. Transfection with GSK-3␣ small interfering RNA (siRNA) and/or GSK-3␤ siRNA mimicked the ability of lithium to induce synergistic protection with VPA. HDAC1 siRNA or other HDAC inhibitors (phenylbutyrate, sodium butyrate or trichostatin A) also caused synergistic neuroprotection together with lithium. Moreover, combination of lithium and HDAC inhibitors potentiated ␤-catenin-dependent, Lef/Tcf-mediated transcriptional activity. An additive increase in GSK-3 serine phosphorylation was also observed in mice chronically treated with lithium and VPA. Together, for the first time, our results demonstrate synergistic neuroprotective effects of lithium and HDAC inhibitors and suggest that GSK-3 inhibition is a likely molecular target for the synergistic neuroprotection. Our results may have implications for the combined use of lithium and VPA in treating bipolar disorder. Additionally, combined use of both drugs may be warranted for clinical trials to treat glutamate-related neurodegenerative diseases.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Synergistic Neuroprotective Effects of Lithium and Valproic Acid or Other Histone Deacetylase Inhibitors in Neurons: Roles of Glycogen Synthase Kinase-3 Inhibition

Leng

Liang²,

Ren³

et al. 2008

J. Neurosci.

198

146

View full text Add to dashboard Cite

show abstract

“…The majority of studies conducted have compared single-drug treatments with placebo or with other single agents. Relatively few reviews have examined the efficacy of anti-manic co-therapy: the concurrent use of antipsychotics and mood stabilizers (3,(7)(8)(9)(10)(11).…”

Section: Introductionmentioning

confidence: 99%

Acute bipolar mania: a systematic review and meta‐analysis of co‐therapy vs. monotherapy

Smith¹,

Cornelius²,

Warnock

et al. 2006

Acta Psychiatr Scand

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Acute bipolar mania: a systematic review and meta-analysis of co-therapy vs. monotherapy Summations• Adjunct treatment with combined antipsychotics and mood stabilizers is more efficacious than mood stabilizers alone.• Combinations of some drugs are less well tolerated than mood-stabilizer monotherapy. Considerations• All studies included subjects who had already failed to respond to mood stabilizers alone.• The quality of study methods and reporting was variable.Smith LA, Cornelius V, Warnock A, Tacchi MJ, Taylor D. Acute bipolar mania: a systematic review and meta-analysis of co-therapy vs. monotherapy.

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“…The effectiveness of antipsychotic medications and drug combinations in LTM studies has not been established yet has become one of the main strategies for clinicians. 1,5,6 This strategy may be inferred from the rapid rise in atypical antipsychotic medication sales and increased use of polypharmacy. [7][8][9][10] It is estimated that nearly half of all BD patients who undergo pharmacological therapy still experience a relapse, accentuating the paucity of effective treatments for this highly diverse, complex illness.…”

Section: Sinopsismentioning

confidence: 99%

Medication-free Alternatives for Long-term Maintenance of Bipolar Disorder: A Case Series

Gurevich¹,

Robinson

2015

Glob Adv Health Med

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Psychopharmacological treatment has been the mainstay in long-term maintenance of bipolar disorder (BD) patients for the last 60 years. Conventionally accepted treatment options are primarily based on expert opinion rather than on well-executed, independently funded research. Investigation of maintaining patients without medications using treatment alternatives has been neglected. This clinical case series examines the outcomes of 7 BD patients who experienced a poor response or significant side effects with conventional treatment modalities. Patients were gradually and safely withdrawn from all medications. Treatment strategies were based on an individualized holistic approach using herbs, nutritional supplements, vitamins, amino acids, acupuncture, dietary recommendations, and behavioral modifications. Multiple treatment modalities were combined addressing the etiological causes for BD symptoms. Upon withdrawal from psychotropic medications, patients were free of medication-induced side effects and obtained psychiatric stability for at least 10 months. Further research is needed to investigate the long-term outcomes of BD treatment modalities based on well-defined successful outcome criteria, such as reduction in symptoms, improvement in quality of life, overall health outcomes, and cost effectiveness.

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Mood Stabilizer Combinations: A Review of Safety and Efficacy

Cited by 185 publications

References 97 publications

Synergistic Neuroprotective Effects of Lithium and Valproic Acid or Other Histone Deacetylase Inhibitors in Neurons: Roles of Glycogen Synthase Kinase-3 Inhibition

Synergistic Neuroprotective Effects of Lithium and Valproic Acid or Other Histone Deacetylase Inhibitors in Neurons: Roles of Glycogen Synthase Kinase-3 Inhibition

Acute bipolar mania: a systematic review and meta‐analysis of co‐therapy vs. monotherapy

Medication-free Alternatives for Long-term Maintenance of Bipolar Disorder: A Case Series

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