Trial reportBipolar disorders2008
Verapamil augmentation of lithium treatment improves outcome in mania unresponsive to lithium alone: preliminary findings and a discussion of therapeutic mechanisms.
Trial report in Bipolar disorders, 2008. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT00518947 (Pharmacotherapy of Treatment-Resistant Mania), which is not on this map. Cited by 15 papers, 2 of them syntheses that pooled it.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Pharmacotherapy of Treatment-Resistant Mania
Who cites it
15 citing papers in PubMed, 2 syntheses or guidelines pooled it, 45 citations in OpenAlex.
- Canadian Network for Mood and Anxiety Treatments (CANMAT) and International Society for Bipolar Disorders (ISBD) 2018 guidelines for the management of patients with bipolar disorder.Bipolar disorders · 2018Guideline
- A systematic review of calcium channel antagonists in bipolar disorder and some considerations for their future development.Molecular psychiatry · 2016Pooled it
- Identifying drug targets for schizophrenia through gene prioritization.Translational psychiatry · 2026Article
- Population Pharmacodynamic Models of Risperidone on PANSS Total Scores and Prolactin Levels in Schizophrenia.Pharmaceuticals (Basel, Switzerland) · 2024Article
- Intracellular Signaling Cascades in Bipolar Disorder.Current topics in behavioral neurosciences · 2021Review
- Aetiology of bipolar disorder: contribution of the L-type voltage-gated calcium channels.General psychiatry · 2019Article
- Role of Protein Kinase C in Bipolar Disorder: A Review of the Current Literature.Molecular neuropsychiatry · 2017Review
- From Gene to Behavior: L-Type Calcium Channel Mechanisms Underlying Neuropsychiatric Symptoms.Neurotherapeutics : the journal of the American Society for Experimental NeuroTherapeutics · 2017Review
- Monotherapy With Major Antihypertensive Drug Classes and Risk of Hospital Admissions for Mood Disorders.Hypertension (Dallas, Tex. : 1979) · 2016Article
- Future Directions for Pharmacotherapies for Treatment-resistant Bipolar Disorder.Current neuropharmacology · 2015Review
- Comparative study of electrocardiographic changes in patients of acute mania receiving verapamil or lithium carbonate.Journal of clinical and diagnostic research : JCDR · 2014Article
- CACNA1C (Cav1.2) in the pathophysiology of psychiatric disease.Progress in neurobiology · 2012Review
- Verapamil results in increased blood levels of oncolytic adenovirus in treatment of patients with advanced cancer.Molecular therapy : the journal of the American Society of Gene Therapy · 2012Article
- A role for the PKC signaling system in the pathophysiology and treatment of mood disorders: involvement of a functional imbalance?Molecular neurobiology · 2011Review
- New therapeutic targets for mood disorders.TheScientificWorldJournal · 2010Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
8 authors at 3 institutions in 1 country.
Funding
Abstract
objectivesAttenuation of protein kinase C (PKC) is a mechanism common to both established (lithium, valproate) and some novel (tamoxifen) antimanic agents. Verapamil, although primarily known as a calcium channel blocker, also has PKC inhibitory activity. Verapamil has shown antimanic activity in some but not all studies. Therefore, we investigated verapamil, used alone or as an adjunctive treatment, in manic patients who did not respond to an initial adequate trial of lithium.
methodsEach study phase lasted three weeks. Subjects were treated openly with lithium in Phase 1 (n = 45). Those who failed to respond were randomly assigned to double-blind treatment in Phase 2 with either verapamil (n = 10) or continued-lithium (n = 8). Phase 2 nonresponders (n = 10) were assigned to combined verapamil/lithium in Phase 3.
resultsResponse in Phase 2 did not differ significantly between verapamil and continued-lithium. During Phase 3, response to combined treatment was significantly better than overall response to monotherapy in Phase 2 (Fisher's Exact test, p = 0.043). Mania ratings improved during combined treatment in Phase 3 by 88.2% (linear mixed model analysis, F = 4.34, p = 0.013), compared with 10.5% improvement during Phase 2.
conclusionsIn this preliminary investigation, verapamil monotherapy did not demonstrate antimanic efficacy. By contrast, the combination of verapamil plus lithium was highly efficacious. Our findings thus suggest that verapamil may have potential utility as an adjunct to lithium. This effect may be mediated by additive actions on PKC inhibition, which may be an important mechanism for antimanic agents in general.
Indexed as
Identifiers
What OpenQuestion holds
Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.