An open trial of pregabalin as an acute and maintenance adjunctive treatment for outpatients with treatment resistant bipolar disorder

Schaffer, Linda C.; Schaffer, Charles B.; Miller, Amber R.; Manley, Jillian L.; Piekut, Jennifer A.; Nordahl, Thomas E.

doi:10.1016/j.jad.2012.09.005

Cited by 30 publications

(17 citation statements)

References 12 publications

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“…27 Pregabalin and gabapentin, both calcium channel modulators, are also top ranked repurposing candidates. Pregabalin has been shown to be an effective adjunctive treatment for MDD 28 and treatment-resistant bipolar disorder, 29 and gabapentin is used off-label for bipolar disorder. 30 The side effect profile of gabapentin includes increased suicidality within the first week of treatment, 31 which is also seen with antidepressant use.…”

Section: Discussionmentioning

confidence: 99%

Using genetic drug-target networks to develop new drug hypotheses for major depressive disorder

Gaspar

Gerring

Hübel

et al. 2018

Preprint

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Number of words in abstract: 197; Number of words in main text: 3292 Number of figures: 3; Number of tables: 2 Number of supplemental information: 3 supplementary texts, 5 supplementary tables, 17 supplementary figures AbstractThe major depressive disorder (MDD) working group of the Psychiatric Genomics Consortium (PGC) has published a genome-wide association study (GWAS) for MDD in 130,664 cases, identifying 44 risk variants. We used these results to investigate potential drug targets and repurposing opportunities. We built easily interpretable bipartite drug-target networks integrating interactions between drugs and their targets, genome-wide association statistics and genetically predicted expression levels in different tissues, using our online tool Drug Targetor (drugtargetor.com). We also investigated drug-target relationships and drug effects on gene expression that could be impacting MDD. MAGMA was used to perform pathway analyses and S-PrediXcan to investigate the directionality of tissue-specific expression levels in patients vs.controls. Outside the major histocompatibility complex (MHC) region, 25 druggable genes were significantly associated with MDD after multiple testing correction, and 19 were suggestively significant. Several drug classes were significantly enriched, including monoamine reuptake inhibitors, sex hormones, antipsychotics and antihistamines, indicating an effect on MDD and potential repurposing opportunities. These findings require validation in model systems and clinical examination, but also show that GWAS may become a rich source of new therapeutic hypotheses for MDD and other psychiatric disorders that need new -and better -treatment options.

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Section: Discussionmentioning

confidence: 99%

Using genetic drug-target networks to develop new drug hypotheses for major depressive disorder

Gaspar

Gerring

Hübel

et al. 2018

Preprint

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“…[79] MDD patients are observed to have deficient stores of vitamin E, [80] higher lipid peroxidation in the brain, [81,82] and oxidative damage to peripherally circulating lipids. [65][66][67][68][69][70] In patients with MDD, the oxidative stress markers in the periphery have been observed to correlate to the duration and severity of the depressive disorder. [82,84,85] Chronic inflammation has been associated with MDD and remission of depression is characterized by a return to more normal inflammatory markers, such as cytokine levels.…”

Section: Depressive Disordersmentioning

confidence: 99%

Exploring the Rationale for the Use of the Ketogenic Diet in the Treatment of Mental Health Disorders

Pergolizzi¹,

Tabor²,

LeQuang³

et al. 2019

obm icm

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Background: The ketogenic diet (KD) was developed in the 1920s as a treatment for pediatric epilepsy and is emerging as a possible treatment option for certain mental health disorders. There is a link between certain mental health disorders and epilepsy, suggesting some commonality among underlying mechanisms. Methods: The literature relating to mental disorders and the KD is sparse. The authors attempt to a narrative review of the existing literature to show that there may be validity to studying the KD as a treatment for certain mental health disorders. Results: Various types of mitochondrial dysfunction and impaired oxidative metabolism have been identified in many mental health disorders (bipolar disorder, major depressive disorder, autism, schizophrenia, and others). Mitochondrial deficits may affect neuroplasticity and cause synaptic dysfunction, which could change brain structure and function in a way that might affect behavior. The KD has been associated with epigenetic changes in the genes associated with mitochondrial function. Chronic oxidative stress and inflammation have also been implicated in mental health disorders and may be reduced by the KD. The KD regulates

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“…There is also some evidence, from an open-label observational study, that pregabalin is effective in the adjunctive treatment of acute mania, depression, and maintenance of refractory bipolar disorder. 20 Gabapentin was originally designed to be structurally similar to the neurotransmitter γ-aminobutyric acid (GABA). 21 It was intended as an antispasmodic drug which would act on GABA receptors and have GABAergic properties.…”

Section: It Wasmentioning

confidence: 99%

Biological rationale and potential clinical use of gabapentin and pregabalin in bipolar disorder, insomnia and anxiety: protocol for a systematic review and meta-analysis

et al. 2017

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IntroductionGabapentin has been extensively prescribed off-label for psychiatric indications, with little established evidence of efficacy. Gabapentin and pregabalin, a very similar drug with the same mechanism of action, bind to a subunit of voltage-dependent calcium channels which are implicated in the aetiopathogenesis of bipolar disorder, anxiety and insomnia. This systematic review and meta-analysis aims to collect and critically appraise all the available evidence about the efficacy and tolerability of gabapentin and pregabalin in the treatment of bipolar disorder, insomnia and anxiety.Methods and analysisWe will include all randomised controlled trials (RCTs) reported as double-blind and comparing gabapentin or pregabalin with placebo or any other active pharmacological treatment (any preparation, dose, frequency, route of delivery or setting) in patients with bipolar disorder, anxiety or insomnia. For consideration of adverse effects (tolerability), single-blind or open-label RCTs and non-randomised evidence will also be summarised. The main outcomes will be efficacy (measured as dichotomous and continuous outcome) and acceptability (proportion of patients who dropped out of the allocated treatment). Published and unpublished studies will be sought through relevant database searches, trial registries and websites; all reference selection and data extraction will be conducted by at least 2 independent reviewers. We will conduct a random-effects meta-analysis to synthesise all evidence for each outcome. Heterogeneity between studies will be investigated by the I2 statistic. Data from included studies will be entered into a funnel plot for investigation of small-study effects. No subgroup analysis will be undertaken, but we will carry out sensitivity analyses about combination treatment, psychiatric comorbidity, use of rescue medications and fixed versus random-effects model.Ethics and disseminationThis review does not require ethical approval. This protocol has been registered on PROSPERO (CRD42016041802). The results of the systematic review will be disseminated via publication in a peer-reviewed journal.

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An open trial of pregabalin as an acute and maintenance adjunctive treatment for outpatients with treatment resistant bipolar disorder

Cited by 30 publications

References 12 publications

Using genetic drug-target networks to develop new drug hypotheses for major depressive disorder

Using genetic drug-target networks to develop new drug hypotheses for major depressive disorder

Exploring the Rationale for the Use of the Ketogenic Diet in the Treatment of Mental Health Disorders

Biological rationale and potential clinical use of gabapentin and pregabalin in bipolar disorder, insomnia and anxiety: protocol for a systematic review and meta-analysis

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