Allopurinol augmentation in the outpatient treatment of bipolar mania: a pilot study

Fan, Alexander H; Berg, A.J.M. van den; Bresee, Catherine; Glassman, Lisa H.; Rapaport, Mark Hyman

doi:10.1111/j.1399-5618.2012.01001.x

Cited by 25 publications

(35 citation statements)

References 17 publications

(23 reference statements)

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“…One study that used a mixed population with some patients entering after a minimum of 2 weeks of mood stabilizer therapy, and others starting a mood stabilizer and risperidone in parallel, provided inconclusive data for risperidone (Yatham et al, 2003) as the results were likely confounded by the effects of carbamazepine on serum levels of risperidone. Allopurinol was not beneficial in patients refractory to lithium, valproic acid, carbamazepine, or atypical antipsychotic medications (Fan et al, 2012), although there are some data suggesting a beneficial effect on patients refractory to valproate (Jahangard et al, 2014). Adding the melatonin agonist ramelteon was also not efficacious in patients refractory to treatment as usual (McElroy et al, 2010b).…”

Section: Efficacy Datamentioning

confidence: 99%

The International College of Neuro-Psychopharmacology (CINP) Treatment Guidelines for Bipolar Disorder in Adults (CINP-BD-2017), Part 2: Review, Grading of the Evidence, and a Precise Algorithm

Fountoulakis

Yatham

Grunze

et al. 2016

IJNPPY

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Background:The current paper includes a systematic search of the literature, a detailed presentation of the results, and a grading of treatment options in terms of efficacy and tolerability/safety.Material and Methods:The PRISMA method was used in the literature search with the combination of the words ‘bipolar,’ ‘manic,’ ‘mania,’ ‘manic depression,’ and ‘manic depressive’ with ‘randomized,’ and ‘algorithms’ with ‘mania,’ ‘manic,’ ‘bipolar,’ ‘manic-depressive,’ or ‘manic depression.’ Relevant web pages and review articles were also reviewed.Results:The current report is based on the analysis of 57 guideline papers and 531 published papers related to RCTs, reviews, posthoc, or meta-analysis papers to March 25, 2016. The specific treatment options for acute mania, mixed episodes, acute bipolar depression, maintenance phase, psychotic and mixed features, anxiety, and rapid cycling were evaluated with regards to efficacy. Existing treatment guidelines were also reviewed. Finally, Tables reflecting efficacy and recommendation levels were created that led to the development of a precise algorithm that still has to prove its feasibility in everyday clinical practice.Conclusions:A systematic literature search was conducted on the pharmacological treatment of bipolar disorder to identify all relevant random controlled trials pertaining to all aspects of bipolar disorder and graded the data according to a predetermined method to develop a precise treatment algorithm for management of various phases of bipolar disorder. It is important to note that the some of the recommendations in the treatment algorithm were based on the secondary outcome data from posthoc analyses.

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Section: Efficacy Datamentioning

confidence: 99%

The International College of Neuro-Psychopharmacology (CINP) Treatment Guidelines for Bipolar Disorder in Adults (CINP-BD-2017), Part 2: Review, Grading of the Evidence, and a Precise Algorithm

Fountoulakis

Yatham

Grunze

et al. 2016

IJNPPY

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“…A similar trial with allopurinol (300mg/day) as an add-on to lithium and haloperidol showed similar results (Akhondzadeh et al, 2006). In addition, a recent pilot study of allopurinol in BD subjects showed that those with restricted caffeine use compared to caffeine users had better outcomes (Machado-Vieira et al, 2008; Fan et al, 2012). It should be noted, however, that this study was small, and that participants were taking a complex medication regimen that included antipsychotics, anticonvulsants, antidepressants, lithium, benzodiazepines, and hypnotics; poor compliance and potential substance abuse were issues of additional concern (Fan et al, 2012).…”

Section: Treatment-related Studies and Clinical Trialsmentioning

confidence: 99%

“…In addition, a recent pilot study of allopurinol in BD subjects showed that those with restricted caffeine use compared to caffeine users had better outcomes (Machado-Vieira et al, 2008; Fan et al, 2012). It should be noted, however, that this study was small, and that participants were taking a complex medication regimen that included antipsychotics, anticonvulsants, antidepressants, lithium, benzodiazepines, and hypnotics; poor compliance and potential substance abuse were issues of additional concern (Fan et al, 2012). Another recent study found no difference between allopurinol (at a lower dose, 300mg/day) and placebo in BD patients experiencing an acute manic episode.…”

Section: Treatment-related Studies and Clinical Trialsmentioning

confidence: 99%

Purinergic system dysfunction in mood disorders: a key target for developing improved therapeutics

Ortiz

Ulrich

Zarate

et al. 2015

Progress in Neuro-Psychopharmacology and Biological Psychiatry

105

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Uric acid and purines (such as adenosine) regulate mood, sleep, activity, appetite, cognition, memory, convulsive threshold, social interaction, drive, and impulsivity. A link between purinergic dysfunction and mood disorders was first proposed a century ago. Interestingly, a recent nationwide population-based study showed elevated risk of gout in subjects with bipolar disorder (BD), and a recent meta-analysis and systematic review of placebo-controlled trials of adjuvant purinergic modulators confirmed their benefits in bipolar mania. Uric acid may modulate energy and activity levels, with higher levels associated with higher energy and BD spectrum. Several recent genetic studies suggest that the purinergic system particularly the modulation of P1 and P2 receptor subtypes—plays a role in mood disorders, lending credence to this model. Nucleotide concentrations can be measured using brain spectroscopy, and ligands for in vivo positron emission tomography (PET) imaging of adenosine (P1) receptors have been developed, thus allowing potential target engagement studies. This review discusses the key role of the purinergic system in the pathophysiology of mood disorders. Focusing on this promising therapeutic target may lead to the development of therapies with antidepressant, mood stabilization, and cognitive effects.

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“…However, controversies also exist: two negative studies failed to show a benefit of adding allopurinol in mania (Fan et al, 2012;Weiser et al, 2014); Salvadore et al, 2010 failed to confirm a correlation between serum uric acid levels and YMRS scores in manic subjects.…”

Section: Introductionmentioning

confidence: 95%

Increased uric acid levels in bipolar disorder subjects during different phases of illness

Albert

Cori

Aguglia

et al. 2015

Journal of Affective Disorders

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Allopurinol augmentation in the outpatient treatment of bipolar mania: a pilot study

Cited by 25 publications

References 17 publications

The International College of Neuro-Psychopharmacology (CINP) Treatment Guidelines for Bipolar Disorder in Adults (CINP-BD-2017), Part 2: Review, Grading of the Evidence, and a Precise Algorithm

The International College of Neuro-Psychopharmacology (CINP) Treatment Guidelines for Bipolar Disorder in Adults (CINP-BD-2017), Part 2: Review, Grading of the Evidence, and a Precise Algorithm

Purinergic system dysfunction in mood disorders: a key target for developing improved therapeutics

Increased uric acid levels in bipolar disorder subjects during different phases of illness

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