Charles Bonnet syndrome (CBS) consists of vivid visual hallucinations which occur in otherwise psychologically normal people with insight. We reviewed the literature associated with pharmacotherapy for CBS. According to the limited data, antipsychotics such as risperidone, mood stabilizers such as valproate, antidepressants such as mirtazapine and Chinese medicine such as Yi-gan san are candidate treatments for visual hallucinations. Since existing data is solely derived from case reports, further controlled studies are required to establish pharmacotherapy for CBS.
Serotonin norepinephrine reuptake inhibitors (SNRIs) work by inhibiting the reuptake of the neurotransmitters serotonin and norepinephrine. This results in an increase in the extracellular concentrations of serotonin and norepinephrine and therefore an increase in neurotransmission. The three SNRIs milnacipran, duloxetine, and venlafaxine have different affinity and selectivity profiles. Milnacipran and duloxetine inhibit the reuptake of serotonin and norepinephrine at all doses. In contrast, venlafaxine selectively inhibits the reuptake of serotonin at low doses, but this serotonin transporter specificity disappears as the dose increases (i.e., it acts as an SNRI). In addition, the SNRIs, as well as the SSRIs, have few significant side effects because they interact only infrequently with other neurotransmitter receptors. Milnacipran and duloxetine seem to have fewer side effects and essentially show no cardiovascular toxicity. However, venlafaxine appears the least well-tolerated because of a high incidence of serotonergic adverse events (nausea, sexual dysfunction, withdrawal problems) and dose-dependent hypertension. SNRIs have increased efficacy and good tolerability and are used for the treatment of anxiety disorders and chronic pain. Our results suggest that SNRIs may have more advantages than other kinds of antidepressants and that the differences in the pharmacological profiles of each should be understood when using them.
Purpose: Hyperprolactinemia, a common adverse effect of antipsychotics, frequently impacts patients' quality of life. Aripiprazole is a potent dopamine D2 receptor partial agonist and rarely increases the serum prolactin concentration. The authors investigated the effect of aripiprazole coadministration on antipsychotic-induced hyperprolactinemia and associated symptoms in patients with schizophrenia. Method: The subjects were 9 patients (8 females, 1 male) with hyperprolactinemia induced by risperidone, olanzapine, haloperidol, zotepine, bromperidol, levomepromazine, and quetiapine; 6 of the females had oligomenorrhea and 2 amenorrhea, and the male had erectile dysfunction. All of the patients received concomitant aripiprazole for more than 8 weeks at a mean dose (range) of 7.7 (3-18) mg/day. The doses of all other medications, including the hyperprolactinemia-inducing antipsychotics, remained fixed throughout the study period. Results: The mean serum concentration (range) of prolactin during aripiprazole coadministration (29.9 (9.8-53) ng/ml) was significantly (p=0.008) lower than that before aripiprazole coadministration (81.1(27-153) ng/ml). The associated symptoms were improved in 4 females (regularized or regained menstruation) and the male (normalized erectile function), while no changes were observed in the other clinical symptoms of schizophrenia. Discussion: The results of the present study suggest that even small doses of coadministered aripiprazole effectively limit excessive prolactin response to antipsychotics without interfering with the benefits of existing prescriptions.
Purpose: Affective temperaments have been suggested to predispose individuals to mood disorders, which can modify their psychopathology and response to treatment. This study aimed to obtain background data on the distributions of and associations among the temperaments, together with their relationships to age and gender, in non-clinical Japanese subjects. Methods: The brief version of the Temperament Evaluation of Memphis, Pisa, Paris and San Diego-autoquestionnaire (TEMPS-A) and the Munich Personality Test (MPT) were administered to 278 healthy volunteers (154 males and 124 females 18-63 years of age). The former contains 39 questions assessing cyclothymic, hyperthymic, irritable, anxious and depressive temperaments, whereas the latter consists of 16 items measuring schizoid and melancholic type temperaments. Results: The proportions of dominant temperaments (greater than the mean + 2SD) were 6.1% for depressive, 3.6% for cyclothymic and schizoid, 2.9% for irritable and anxious, 2.5% for melancholic, and 1.8% for hyperthymic. Strong correlations were found among four temperaments -- cyclothymic, irritable, depressive and schizoid (rs > 0.5, except for a value of 0.435 for the schizoid-depressive correlation) -- while hyperthymic, anxious and melancholic temperaments had modest satellite linkages with these four core temperaments. Age was moderately correlated with cyclothymic temperament (rs = -0.355, p = 0.001) and weakly correlated with melancholic, depressive and irritable temperaments. Females were more likely to have cyclothymic and anxious temperaments, while males were more likely to have hyperthymic and schizoid temperaments. Discussion: Close correlations among temperaments suggest that individualized treatment strategies should be implemented depending on the psychopathology of the individual, which could be affected by combined temperaments. Young and female individuals are more likely to have cyclothymic temperaments, suggesting that these subjects should be more likely to exhibit bipolarity.
Purpose: The purpose of this study is to compare the steady-state plasma levels of HAL between Japanese, Koreans and Swedes who were treated with HAL monotherapy per os. Method: The steady-state plasma levels of haloperidol (HAL) in 75 Japanese, 120 Korean, and 50 Swedish psychiatric patients treated orally with HAL were compared. Results: Significantly higher doses of HAL were used in the Koreans (mean dose = 21 mg/day) than in the Japanese (15 mg/day) or Swedes (9 mg/day) (one-way analysis of variance (ANOVA) (p<0.0001), Bonferroni's post test (p<0.001)). The mean concentration/daily dose ratio (C/D ratio) of HAL was 2.2 times higher in Korean patients (2.78 nmol/L/mg/day) and 1.5 times higher in Japanese patients (1.88 nmol/L/mg/day) than that in Swedish patients (1.24 nmol/L/mg/day). A significant difference in the C/D ratio was observed among the 3 ethnic groups (one-way ANOVA; p<0.0001). Discussion: The higher C/D ratio of HAL in Asians might be partly due to the higher frequency of the CYP2D6*10 allele in Asians; however, interethnic differences in the activity of other enzymes, such as CYP3A4, might have caused the differences in the present study, especially at the higher doses of HAL.
Purpose: A number of depressed patients do not respond adequately to standard antidepressant treatments, and some of them subsequently suffer from treatment-resistant mood disorder (TRMD). Lamotrigine (LTG) is the only mood stabilizer that is effective for preventing depressive episodes of bipolar disorders. This study aimed to evaluate the efficacy of LTG augmentation in Japanese patients with TRMD. Methods: The subjects were 30 patients with refractory depression who had already shown insufficient response to multiple pharmacotherapy including antidepressants, mood stabilizers and atypical antipsychotics. The diagnoses were major depressive disorder (n=16), bipolar disorder (n=10) and dysthymic disorder (n=4). All patients gave written informed consent to receive LTG as an off-label indication in Japan after explanation for possible risks of unwanted skin reactions. The daily dose of LTG was titrated by the clinician's decision (88.0±61.9 mg/day). Treatment response was assessed by Montgomery-Åsberg Depression Rating Scale (MADRS) and Global Assessments of Functioning (GAF) before and after the 8-week LTG augmentation. Results: Significant improvements were observed in the scores of MADRS (25.3±10.1 → 14.7±10.5) and GAF (49.2±12.3 → 64.1±11.7) after the 8-week LTG augmentation (p=0.0010). Greater number of the past mood episodes and shorter duration of the present depressive episode are associated with better response to LTG. Mild adverse skin reactions developed in 10 patients although 8 out of them were treatment responders. Discussion: LTG augmentation may be effective for the treatment of TRMD, especially with shorter duration of unremitted depression and more recurrent episodes. However, attention should be paid to the development of adverse skin reactions in LTG responders.
Purpose: Antipsychotic polypharmacy has been utilized frequently in the clinical setting despite lack of evidence for its safety or efficacy. In an effort to promote the optimal use of antipsychotic medication, we examined the current state of antipsychotic polypharmacy and the use of excessive doses in outpatients with schizophrenia. Method: The subjects of this study were schizophrenia patients who received oral antipsychotic medications from 1997 to 2007. The patient characteristics and prescription profiles, as well as the dosages, for all medications were obtained from the patients' medical charts. Psychotropic medications were classified into five categories: antipsychotics, antiparkinsonian agents, anxiolytics/sedative hypnotics, antidepressants, and mood stabilizers. The frequency of use and the equivalent doses of each psychotropic drug were summarized and used for correlation analysis. This study was approved by the Ethics Committee of the Nagoya University Graduate School of Medicine. Results: Sixty-four percent of patients on antipsychotic pharmacotherapy received a single antipsychotic drug, and 36% received two or more. Among the 527 patients on monotherapy, 53.5% were prescribed first-generation antipsychotics (FGAs) and 46.5% were prescribed second-generation antipsychotics (SGAs) in the period from 1997 through 2007. Positive correlations between antipsychotics and antiparkinsonian agents were obtained both for the number of drugs (p < 0.01) and the equivalent dosage (p < 0.01); the prescribing rate for antiparkinsonian agents, however, fell significantly from 1997 to 2007 (p < 0.0001). Discussion: These results suggest that the frequency with which antiparkinsonian agents are combined has also decreased due to the increase in the rate at which SGAs are prescribed. Greater awareness among psychiatrists at Nagoya University Hospital of the proper use of antipsychotics has resulted in a reduced prevalence of antipsychotic polypharmacy and less frequent use of excessive dosages.
Chronic pain complaints are common among patients with major depression, and patients with physical pain are more likely to develop major depression. Antidepressants are effective against both pain and the symptoms of depression, but the use of these agents for treating patients with bipolar disorder is problematic because of the significant risk of inducing mania. In the present case, a patient with bipolar depression suffering from chronic pain had been misdiagnosed with major depressive disorder and treated with antidepressants for several years. His pain improved dramatically after the administration of lithium, and he remained free of pain despite the discontinuation of treatment with antidepressants. This suggests that lithium might be more useful than antidepressants for the treatment of bipolar depression with chronic pain. Further research is needed to compare the effectiveness of lithium to that of other mood stabilizers such as valproate, carbamazepine, and lamotrigine in order to identify treatment strategies for patients with bipolar disorder associated with chronic pain.