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Dopamine supersensitivity psychosis (DSP) is observed in patients with schizophrenia under antipsychotic treatment, and it is characterized by rebound psychosis, an uncontrollable psychotic episode following a stable state and tardive dyskinesia. DSP, first described in patients taking typical antipsychotics in the late 1970s, sometimes appears even in patients who are treated with current atypical antipsychotics. It was recently demonstrated that DSP can have a negative impact on the long-term prognosis of schizophrenia patients and that DSP could be involved in the etiology of some cases of treatment-resistant schizophrenia. Accumulating evidence suggests that an up-regulation of dopamine D2 receptors (DRD2) in the brain caused by long-term exposure to antipsychotics is related to the DSP phenomenon. The present review describes the clinical characteristics and the etiology of DSP in the era of second-generation antipsychotics for patients with schizophrenia. Based on the mechanism of DSP, several potential treatments for patients presenting with a DSP episode or the dopamine supersensitivity state are also discussed. [ABSTRACT FROM AUTHOR]

Elderly patients are vulnerable to the adverse neurological effects of antipsychotics, particularly Parkinsonian symptoms and tardive dyskinesia. This vulnerability in the elderly becomes complex and unpredictable when aripiprazole is prescribed to replace other second-generation or first-generation antipsychotics. This report describes a 69-year-old female schizophrenic patient, who received aripiprazole after using a few antipsychotics, including the first- and second-generation ones. The tardive dyskinesia developed 6 weeks after switching to aripiprazole but subsided 4 weeks later when stopping the concurrent amantadine and decreasing the dosage of trihexyphenidyl. However, Parkinsonian symptoms developed insidiously thereafter, which remitted after the dosage of trihexyphenidyl was increased again. The possible mechanisms of the alternated adverse neurological events after a switch to aripiprazole in the chronic elderly psychosis are discussed.

The administration of aripiprazole (ARI), a dopamine partial agonist, could provoke abrupt psychotic worsening in patients with schizophrenia. We explored the relationship between this psychotic worsening and dopamine supersensitivity psychosis (DSP), which is a clinically vulnerable state. We conducted a retrospective investigation for 264 patients whose treatment medication was switched to ARI from other antipsychotics. We divided the patients into the DSP(+) group with a history of DSP episode(s) (N = 70) and the DSP(–) group without such a history (N = 194), and then compared the clinical factors relevant to the success or failure of the switch to ARI between them. The results revealed that patients in the DSP(+) group experienced psychotic worsening following the switch to ARI with a significant higher rate compared to the DSP(–) group (23% vs. 8%, P < 0.01). Moreover, the dosages of the drugs before the ARI introduction in the patients experiencing the psychotic worsening in the DSP (-) group were higher than those in other patients of the group. Our findings suggest that patients who receive high dosages of antipsychotic drugs form overt or covert DSP and such state is highly associated with psychotic worsening following ARI treatment. [ABSTRACT FROM AUTHOR]

Abstract: The in vivo labeling and brain imaging of dopamine transporters measure the density of dopamine neuron terminals in the human caudate/putamen. A review of such studies shows that the long-term use of antipsychotics had no major effect on the density of the dopamine terminals in individuals who had no tardive dyskinesia, but had reduced the density in those patients with tardive dyskinesia. In addition, the normal loss of dopamine terminals in healthy individuals was approximately 5% per decade. However, this rate of cell loss was apparently increased by approximately three-fold, to about 15% per decade, in schizophrenia patients using antipsychotics on a long-term basis, as measured by the in vivo imaging of the dopamine transporters in the dopamine neuron terminals. While an apparent reduction in dopamine transporters may result from reduced expression of the transporters secondary to antipsychotic treatment, the seemingly increased loss rate is consistent with the accumulation of antipsychotics in the neuromelanin of the substantia nigra, subsequent injury to the dopamine-containing neurons, and the development of extrapyramidal motor disturbances such as tardive dyskinesia or Parkinson's disease. [Copyright &y& Elsevier]

Summary: Elderly patients are vulnerable to the adverse neurological effects of antipsychotics, particularly Parkinsonian symptoms and tardive dyskinesia. This vulnerability in the elderly becomes complex and unpredictable when aripiprazole is prescribed to replace other second-generation or first-generation antipsychotics. This report describes a 69-year-old female schizophrenic patient, who received aripiprazole after using a few antipsychotics, including the first- and second-generation ones. The tardive dyskinesia developed 6 weeks after switching to aripiprazole but subsided 4 weeks later when stopping the concurrent amantadine and decreasing the dosage of trihexyphenidyl. However, Parkinsonian symptoms developed insidiously thereafter, which remitted after the dosage of trihexyphenidyl was increased again. The possible mechanisms of the alternated adverse neurological events after a switch to aripiprazole in the chronic elderly psychosis are discussed. [ABSTRACT FROM AUTHOR]

Introduction: Chronic treatment with dopamine D2 receptor antagonists has been proposed to lead to dopamine receptor supersensitivity. Frequently, this is conceptualized as upregulation or changes in the structure or function of the post-synaptic D2 receptor. However, the measured 1.4-fold increase in D2 receptor density and the lack of actual receptor supersensitivity are probably inadequate to explain outcomes such as tardive dyskinesia (TD) and dopamine supersensitivity psychosis.Hypothesis: Recent data suggest that TD may result from a combination of presynaptic, synaptic, and postsynaptic changes.Discussion: Presynaptic increase in dopamine release occurs when super-therapeutic blockade of postsynaptic D2 receptors results in excess synaptic unbound dopamine which ultimately ends up being reuptaken by the presynaptic neuron through the dopamine transporter. The increased availability of recycled dopamine results in higher vesicular dopamine concentrations. Since the quantity of neurotransmitter released (known as quanta) is determined by the number of presynaptic neurotransmitter vesicles, the increase in the number (concentration) of dopamine molecules in the vesicles results in a higher concentration of synaptic dopamine with successive depolarization events. Synaptic changes such as the appearance of perforated synapses which is an early step in new synapse formation have been shown in animal models of TD. Finally, postsynaptic increases in D2 receptor expression without demonstration of increased sensitivity or potency has been demonstrated.Conclusion: TD likely develops due to changes across the synapse and terminology such as 'dopamine receptor supersensitivity' can be misleading. 'Synaptic upregulation' may be a more correct term. [ABSTRACT FROM AUTHOR]