Background: Patients with first-episode psychosis respond well to initial antipsychotic treatment, but among patients experiencing a relapse of psychosis, the response rate falls to approximately 30%. The mechanism of this discrepancy has not been clarified, but the development of dopamine supersensitivity psychosis with the underlying up-regulation of post-synaptic dopamine D2 receptors could be involved in this lesser response. It is uncertain whether elevated dopamine synthesis and release occurs in patients with dopamine supersensitivity psychosis, in contrast to those with first-episode psychosis. Patients and methods: We examined a first-episode psychosis group ( n=6) and a chronic schizophrenia group, i.e. patients experiencing relapse ( n=23) including those who relapsed due to dopamine supersensitivity psychosis ( n=18). Following the initiation of treatment, we measured the patients’ blood concentrations of homovanillic acid and 3-methoxy-4-hydroxyphenylglycol at two weeks and four weeks after the baseline measurements. Results: The first-episode psychosis group tended to show decreased homovanillic acid, accompanied by an improvement of symptoms. The chronic schizophrenia group showed no alteration of homovanillic acid or 3-methoxy-4-hydroxyphenylglycol over the treatment period. These results were the same in the dopamine supersensitivity psychosis patients alone. Conclusions: Our findings suggest that unlike first-episode psychosis, the release of dopamine from presynaptic neurons did not increase in relapse episodes in the patients with dopamine supersensitivity psychosis. This indirectly indicates that the development of supersensitivity of post-synapse dopamine D2 receptor is involved in relapse in dopamine supersensitivity psychosis patients.

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Patients with schizophrenia experiences varying clinical courses in the symptoms and up to 30-60% of patients with schizophrenia do not respond sufficiently to antipsychotics. Treatment-resistant Schizophrenia (TRS) can have several reasons, including early onset, nonadherence to oral medication regimens, and persistent negative symptoms known as deficit syndrome. Patients with TRS experience frequent exacerbations, leading to the need for higher doses of antipsychotics to achieve a clinical result.Recently, dopamine supersensitivity psychosis (DSP) and tardive dyskinesia (TD), both of which could be caused by inappropriate pharmacotherapy, as typified by excessive dosages of antipsychotics, have also been presumed relevant to TRS. Several lines of evidence suggest that both DSP and withdrawal psychosis are closely linked to the supersensitivity of dopamine D2 receptors; this could be caused by a potent blockade of the receptors by antipsychotics. Indeed our study recently has found that patients with DSP are overlapped with the concept of treatment-resistance, and these patients can be recovered by long-acting injectable form, via amelioration of Dopamine supersensitivity state. However, it was also observed that one group did not improve at the clinical symptomatic level, despite the presence of DSP.Here, we try to verify relation in patients with treatment-resistant schizophrenia between several classes of antipsychotics or clinical symptoms and treatment process with oral antipsychotics after the initiation of RLAI. This study is a naturalistic, one-arm design with a 12-month observation period of a moderate sample size (N=115).