The role of selegiline in the treatment of negative symptoms associated with schizophrenia

School of Pharmacy, University of Missouri-Kansas City, Kansas City, MO 64108, USA.
Annals of Pharmacotherapy (Impact Factor: 2.92). 06/2007; 41(5):851-6. DOI: 10.1345/aph.1H556
Source: PubMed

ABSTRACT To evaluate the role of selegiline in the treatment of negative symptoms associated with schizophrenia.
MEDLINE (1966-January 2007) and PsychINFO (1967-January 2007) were searched, using the terms schizophrenia, negative symptoms, and selegiline. A bibliographic search was conducted, as well.
All English-language articles identified from the search were evaluated. All primary literature was included in the review.
Based on its dopamine-enhancing property, selegiline has been studied as augmentation to antipsychotic therapy for the treatment of negative symptoms associated with schizophrenia. The efficacy of low-dose oral selegiline for the treatment of negative symptoms has been evaluated in 1 case report, 2 open-label trials, and 2 controlled trials. The case report and both open-label trials report improvement of negative symptoms associated with low-dose oral selegiline. In 1 of the controlled trials, selegiline showed no difference in effect from that of placebo. These data are limited by small sample sizes. The largest controlled trial demonstrated a statistically significant difference between selegiline and placebo; however, the clinical significance is questionable, given that patients treated with selegiline were still experiencing marked negative symptoms at study completion. No comparative studies evaluating low-dose oral selegiline versus other augmentative treatment options for negative symptoms associated with schizophrenia exist at this time.
Given the limitations of current literature, low-dose oral selegiline cannot be recommended for treatment of negative symptoms associated with schizophrenia. Additional controlled trials are needed to better delineate whether there is a role for selegiline in decreasing the burden of negative symptoms associated with schizophrenia.

  • [Show abstract] [Hide abstract]
    ABSTRACT: Numerous lines of evidence converge to suggest that while dopamine-2 receptor antagonism may be necessary for effective schizophrenia treatment, it is as yet insufficient. Network theory indicates that a number of subtle alterations to biological systems are required to change their output effectively: many candidates for such alteration have arisen through preclinical science. Glutamate modulation is currently very popular but as yet unproven: serotonergic and cholinergic mechanisms are also being utilised in putative antipsychotic development. Most pipeline antipsychotic drugs have an affinity profile distributed across a number of therapeutic targets. In practice the majority of patients are treated with more than monotherapy, but the effectiveness of such regimes is not particularly impressive, certainly in groups of patients: monotherapy continues to be recommended. However, there is an increasing volume of augmentation trials which indicate that additional medications from numerous pharmacological classes may be of assistance in the individual patient if not the group. It is very important to specify and target the residual problematic symptoms when attempting rational polypharmacy, and an exit strategy is essential. The only existing magic shotgun is clozapine which, despite its many drawbacks, continues as the sole effective therapeutic option in treatment resistant illness. New techniques of drug discovery including individual affinity and gene based strategies hold much promise in the design of future antipsychotic drugs. It seems highly unlikely that there will be a magic bullet for schizophrenia: it is to be hoped that some of the magic shotguns in development, both polypharmacy strategies and new antipsychotic drugs, will reach their target eventually. KeywordsSchizophrenia-Magic Shotgun-Polypharmacy-Monotherapy-Dopamine-Glutamate-Serotonin-Drug Discovery-Antipsychotic
    04/2011: pages 23-49;
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Schizophrenia is a chronic and disabling mental disorder characterized by positive, negative and mood symptoms, disturbed coping abilities with elevated distress and a significant decline in cognition, quality of life and psychosocial functioning. About one-third of all patients with schizophrenia do not respond adequately to drug treatment. Today neuroscience and clinical research have sufficiently advanced to introduce a novel generation of compounds with neuroprotective properties. The use of neuroprotective agents in schizophrenia is not yet significantly established. An in-depth review of new compounds such as neurosteroids, estrogen, omega-3 fatty acids, S-adenosylmethionine, cannabinoids, piracetam, modafinil, L-theanine, bexarotene with neuroprotective properties is discussed. The mechanisms underlying the neuroprotective effects of these compounds vary and differ from classically defined dopamine and serotonin receptors. This review highlights selective evidence supporting a neuroprotective approach in the search for novel compounds, and suggests future directions for this exciting area. Neuroprotection strategy may be a useful paradigm for treatment of prodromal and first-episode schizophrenia patients and might have a significant impact on the subsequent course and outcome of the illness. The clinical effects of neuroprotective agents clearly merit further investigation in schizophrenia spectrum disorders. KeywordsSchizophrenia-Neurodevelopmental model-Neurodegenerative model-Apoptosis-Oxidative stress-Excitotoxicity-Stress sensitization-Neurotrophic factor expression-Alteration of neurosteroids-Vulnerability model-Neurocognitive domains-Quality of life deficit-Neuroprotective agents-Neurosteroids-Pregnenolone-Dehydroepiandrosterone-Bexarotene-Theanine
    12/2009: pages 343-395;
  • Source

Full-text (2 Sources)

Available from
Jun 5, 2014