Impulse control disorder during continuous subcutaneous apomorphine treatment (CAI) was recently reported. We describe a 54-year-old patient with familial Parkinson's disease, who after initiation of CAI in addition to high dose levodopa and amantadine, developed impulse control disorder (major financial loss related to risky transactions and self-medication), psychosis and depression, which lead up to attempted suicide. To our knowledge, this is the first case of attempted suicide under apomorphine treatment.
"There is growing evidence that psychosis and impulse control disorders develop in patients under L-DOPA and dopamine agonist therapy (Pontone et al., 2006; Voon et al., 2006; Struhal et al., 2012). A number of preclinical studies also show that long-term administration of dopamine agonists, as well as L-DOPA, is rewarding and reinforcing and may elicit psychosis-like behavior (Tomiyama et al., 2005; Marston et al., 2009; Ikram and Haleem, 2011; Kotagale et al., 2012; Mahmood et al., 2012). "
[Show abstract][Hide abstract] ABSTRACT: Dysfunctions of the basal ganglia are associated with a number of neurological and psychiatric conditions including Parkinson's disease and schizophrenia. Current treatments of these disorders are mostly symptomatic and inadequate, and are often associated with a number of unwanted side-effects. The striatum, the terminal region of the nigrostriatal dopamine pathway, is the main input nucleus of the basal ganglia, and dopamine neurotransmission through the nigrostriatal pathway plays a crucial role in the modulation of basal ganglia output and mediated behaviors. Evidence suggests a role of 5-hydroxytryptamine (5-HT; serotonin)-1A receptors in the modulation of dopamine neurotransmission and in improving pharmacotherapy in schizophrenia and Parkinson's disease. This review concerns the role of 5-HT1A receptors in the modulation of nigrostriatal dopamine neurotransmission, with the aim of providing guidelines for future research to improve pharmacotherapy. The current state of knowledge suggests that drugs simultaneously targeting dopamine D2 and 5-HT1A receptors may improve pharmacotherapy for schizophrenia and Parkinson's disease. Activation of somatodendritic 5-HT1A receptors in the dorsal raphe nucleus has an important role in the alleviation of extrapyramidal symptoms and levodopa-induced dyskinesia induced by antipsychotic treatment. Drugs acting exclusively through dopamine D2 and 5-HT1A receptors are highly needed to validate the potential role of 5-HT1A receptors in improving therapeutics for Parkinson's disease and schizophrenia.
"While apomorphine and other dopamine receptor agonists act positively in partially restoring the motor deficits elicited by Parkinson's disease, a constellation of addictive syndromes has been also noticed in certain patients. It includes addiction to medications, compulsive behaviors, and disturbances of impulse control (Struhal et al., 2012; Pontone et al., 2006, Voon et al., 2006; Weintraub et al., 2010) Preclinical research also shows that dopamine agonists including apomorphine are rewarding when tested in conditioned place preference (CPP) paradigm (Papp, 1988; Khroyan et al., 1995; Hoffman et al., 1988, Graham et al., 2007; Zengin- Toktas et al., 2013). Development of novel pharmacological agents for the suppression of rewarding effects of apomorphine and other dopamine agonists is therefore important for improving therapeutics in Parkinson's disease (Haleem, 2013). "
[Show abstract][Hide abstract] ABSTRACT: Apomorphine is a non-narcotic derivative of morphine, which acts as a dopamine agonist to produce psychostimulant like effects. Currently, apomorphine is used in patients with advanced Parkinson's disease, for the treatment of persistent and disabling motor fluctuations, but a constellation of addictive syndromes such as excessive over use of medication, compulsive behaviors, and disturbances of impulse control are noticed in certain patients. Research on rodent models using conditioned place preference (CPP) paradigm also shows that the drug is rewarding. Previously we have shown that repeated administration of apomorphine produces behavioral sensitization which is prevented in rats co-injected with a low (1.0 mg/kg) but not higher (2.0 mg/kg) dose of buspirone. The present study shows that rewarding effects of apomorphine (1.0 mg/kg) in a CPP paradigm are also blocked in rats co-injected with a low (1.0 mg/kg) but not higher (2.0 mg/kg) dose of buspirone. The levels of serotonin and its metabolite are decreased in the caudate as well as nucleus accumbens of rats exhibiting CPP and the decreases do not occur in animals co-injected with low or higher dose of buspirone. The levels of dopamine and its metabolites are not affected in animals exhibiting CPP; administration as well as co-administration of higher dose of buspirone decreased dopamine metabolism in the caudate as well as nucleus accumbens. The findings suggest a critical role of serotonin in the rewarding effects of apomorphine and imply that co-use of buspirone at low doses can help to control addictive syndromes in Parkinson's disease patients on apomorphine therapy.
Brain Research 10/2014; 1586. DOI:10.1016/j.brainres.2014.06.022 · 2.84 Impact Factor
"Despite a number of clinically useful effects (Ribaric, 2012), there is growing evidence that psychosis and impulse control disorders develop in patients on apomorphine therapy (Pontone et al., 2006; Voon et al., 2006; Struhal et al., 2012). "
[Show abstract][Hide abstract] ABSTRACT: Despite a number of clinically useful effects, there is growing evidence that psychosis and impulse control disorders develop in patients on apomorphine therapy. Evidence suggests a critical role of serotonin-1A receptors in psychosis, drug abuse, and in the mechanism of action of the prototypical selective serotonin reuptake inhibitor fluoxetine. We investigated whether fluoxetine can prevent apomorphine-induced behavioral sensitization in a rat model of psychosis. Animals treated with fluoxetine (5 and 10 mg/kg) for 2 weeks were subsequently cotreated with apomorphine (1.0 mg/kg) for 7 days. A single injection of apomorphine increased motor activity, whereas repeated daily injections produced a progressive sensitization of motor behavior. The sensitization effects of apomorphine did not occur in fluoxetine-pretreated and subsequently cotreated animals. To further elucidate the mechanism involved in the inhibition of apomorphine sensitization in fluoxetine-treated animals, we found that apomorphine-induced motor behavior was much greater in repeated apomorphine-treated than repeated saline-treated animals. It was also greater in apomorphine and fluoxetine-cotreated animals, but not in animals pretreated and cotreated with fluoxetine. The mechanism involved in the inhibition of apomorphine sensitization in fluoxetine-pretreated animals is discussed. The findings introduce an innovative approach for extending the therapeutic use of apomorphine and classical psychostimulant drugs.
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