Nonsteroidal anti-inflammatory drugs and 5-HT3 serotonin receptor antagonists as innovative antipsychotic augmentation treatments for schizophrenia
Antipsychotic treatment is the mainstay in the management of schizophrenia. However, despite optimum use of antipsychotic drugs, many schizophrenia patients continue to exhibit residual positive, negative, cognitive, and other symptoms. Various antipsychotic augmentation strategies have been studied using non-antipsychotic augmenting agents; 2 innovative classes of drugs examined have been nonsteroidal anti-inflammatory drugs (NSAIDs) and 5-HT₃ serotonin receptor antagonists. Meta-analysis of the NSAID studies in schizophrenia patients with positive symptoms (8 randomized controlled trials [RCTs], pooled N = 774) shows that NSAID augmentation is associated with a significant decrease in positive symptom ratings (standardized mean difference [SMD] = 0.19), with no significant change in negative or total symptom ratings. Meta-analysis of the 5-HT₃ antagonist studies in stable schizophrenia patients (6 RCTs, pooled N = 311) shows that 5-HT₃ antagonist augmentation is associated with significant reduction in negative symptom (SMD = 1.10), general psychopathology (SMD = 0.70), and total symptom (SMD = 1.03) ratings without reduction in positive symptom ratings. Neither NSAID nor 5-HT₃ antagonist augmentation increases the dropout rate. Whereas the benefits with NSAID augmentation are, perhaps, too small to be clinically meaningful, antipsychotic augmentation with 5-HT₃ antagonists may be a possible strategy to reduce persistent negative symptoms in schizophrenia. Both fields of inquiry require further investigation.
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ABSTRACT: Antidepressant augmentation strategies are commonly employed to treat depressed patients who do not respond to antidepressant monotherapy. Neuroinflammatory mechanisms have been implicated in depression, and nonsteroidal anti-inflammatory drugs (NSAIDs) have been found effective in animal models of depression both in monotherapy and when used to augment antidepressant drugs. However, results with NSAIDs have been mixed in human observational studies, with both better and worse depression outcomes reported. Four small (pooled N = 160) randomized controlled trials suggest that celecoxib (200-400 mg/d) augmentation of antidepressant medication improves 4-6 week outcomes in major depressive disorder. There are no data, however, to support the use of celecoxib or other NSAIDs in antidepressant-resistant depression. There are also concerns about adverse events associated with NSAID treatment, and about pharmacodynamic drug interactions between these drugs and serotonin reuptake inhibitors. A reasonable conclusion for the present is that NSAID augmentation of antidepressants is, at best, a tentative approach in nonrefractory major depression.
The Journal of Clinical Psychiatry 09/2014; 75(9):975-977. DOI:10.4088/JCP.14f09432 · 5.50 Impact Factor
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ABSTRACT: Serotonin reuptake inhibitors (SRIs) are the mainstay in the treatment of obsessive-compulsive disorder (OCD). Patients who do not respond adequately to SRIs commonly receive augmentation therapy with another agent, usually an atypical antipsychotic drug. Atypical antipsychotics, however, may not be appropriate for or acceptable to all patients. Ondansetron is an experimental alternative for such patients. There have been at least 6 trials that have examined a short-term (8-12 weeks) role for ondansetron in patients with OCD. These include 1 placebo-controlled crossover trial (N = 11); 1 uncontrolled monotherapy trial (N = 8); 2 low-dose (0.5-1.0 mg/d), uncontrolled augmentation trials in patients who did not respond adequately to ongoing or earlier treatments (pooled N = 35); and 2 moderate- to high-dose (4-8 mg/d) randomized, placebo-controlled augmentation trials in patients with undocumented past treatment history (pooled N = 88). Ondansetron was modestly effective in the uncontrolled trials and strikingly effective in the controlled trials. Ondansetron was also very well tolerated in all of the studies. These enthusiastic observations must be tempered by the limitations of the reviewed data, such as small sample sizes, short study durations, lack of data on the effects of blinded ondansetron discontinuation, lack of long-term data, and study-specific limitations. At best, ondansetron (1-8 mg/d) may be considered an experimental SRI augmentation agent in OCD patients for whom augmentation with an atypical antipsychotic drug is problematic.
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The Journal of Clinical Psychiatry 01/2015; 76(1):e72-5. DOI:10.4088/JCP.14f09704 · 5.50 Impact Factor
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