Prescribing Pattern of Antidepressants in Children and Adolescents: Findings from the Research on Asia Psychotropic Prescription Pattern.

OBJECTIVE: Pharmacotherapy of depression in children and adolescents is complex. In the absence of research into the efficacy and safety of antidepressants in this group of patients, their off-label prescription is common. This paper aimed to illustrate the prescription pattern of antidepressants in children and adolescents from major psychiatric centres in Asia. METHODS: The Research on Asia Psychotropic Prescription Pattern on Antidepressants worked collaboratively in 2013 to study the prescription pattern of antidepressants in Asia using a unified research protocol and questionnaire. Forty psychiatric centres from 10 Asian countries / regions participated and 2321 antidepressant prescriptions were analysed. RESULTS: A total of 4.7% antidepressant prescriptions were for children and adolescents. Fluoxetine, sertraline, and escitalopram were the most common antidepressants prescribed for children and adolescents. Almost one-third (30.3%) of prescriptions were for diagnoses other than depressive and anxiety disorders. There was less antidepressant polypharmacy and concomitant use of benzodiazepine, but more concomitant use of antipsychotics in children and adolescents compared with adults. CONCLUSION: Off-label use of antidepressants in children and adolescents was reported by 40 Asian psychiatric institutions that participated in the study. In-service education and regulatory mechanisms should be reinforced to ensure efficacy and safety of antidepressants in children and adolescents.

Antidepressant Prescription Pattern in the Presence of Medical Co-morbidity: REAP-AD 2013 Study.

OBJECTIVE: To evaluate the prescription pattern of antidepressants in patients with medical co-morbidity from major psychiatric centres in Asia. METHODS: The Research on Asian Psychotropic Prescription Pattern for Antidepressants (REAP-AD 2013) collected data from 42 psychiatric centres in 10 Asian countries and regions. Antidepressant prescriptions of 2320 patients with various psychiatric disorders were evaluated. Of these, 370 patients who had specified medical co-morbidities formed the study cohort. RESULTS: Escitalopram (20%) and mirtazapine (20%) were the most commonly prescribed antidepressants in patients with medical co-morbidity followed by sertraline (16%), trazodone (15%), and paroxetine (12%). Overall, more than half (52%; 247/476) of prescriptions comprised selective serotonin reuptake inhibitors. Slightly less than two-thirds (63%; n = 233) of patients received at least 1 selective serotonin reuptake inhibitor. In addition, 79% of patients were prescribed only 1 antidepressant. The mean number of antidepressants used per patient was 1.25 (standard deviation, 0.56). There were subtle differences in the most preferred antidepressant across medical illnesses such as diabetes mellitus, liver dysfunction, acid peptic disease, and cerebrovascular disease. Differences were also seen in prescription patterns across different countries. CONCLUSION: Although selective serotonin reuptake inhibitors formed the bulk of antidepressant prescriptions in the presence of medical co-morbidity, mirtazapine was also commonly used in the presence of medical co-morbidities. Specified medical morbidities do influence the selection of antidepressants.

TJS-010, a new prescription of oriental medicine, enhances 8-OH-DPAT-induced effects in rats.

We evaluated the effect of TJS-010, a new prescription of oriental medicine, on hypothermia and flat body posture in rats, induced by activation of serotonin (5-HT)-1A receptors by (+/-)-8-hydroxy-2-(di-N-propylamino)-tetralin (8-OH-DPAT). Hypothermia was induced by 8-OH-DPAT in a dose and time-dependent manner. The hypothermia induced by 0.1 mg/kg 8-OH-DPAT was enhanced by 500 and 750 mg/kg of TJS-010. At the concentration of 0.1 mg/kg, 8-OH-DPAT also produced flat body posture in rats, and 750 mg/kg TJS-010 increased the flat body posture. These results suggest that TJS-010 facilitates the 5-HT-1A receptors in the central nervous system.

TJS-010, a new prescription of oriental medicine, antagonizes tetrabenazine-induced suppression of spontaneous locomotor activity in rats.

1. The authors have determined the effect of TJS-010, a new prescription of oriental medicine, on the locomotor activity in rats. 2. Tetrabenazine(TBZ) decreased the spontaneous locomotion in rats, and attenuated the contents of amines and increased their metabolism in various regions in rat brain. 3. TJS-010 inhibited the locomotor suppression induced by TBZ: however, neither amine contents nor their metabolism was not altered, which suggested that TJS-010 postsynaptically modulated the transmission or transduction. 4. Imipramine also inhibited the decrease in locomotion induced by TBZ. 5. These results suggest a possibility that TJS-010 has an antidepressive effect.

TJS-010, a new prescription of Kampo medicine with putative antidepressive and anxiolytic properties.--A behavioral study using experimental models for depression and anxiety.

We investigated the effect of TJS-010, a new prescription of Kampo or oriental medicine, on the locomotor activity and body temperature in rats in order to determine its antidepressive and anxiolytic effects. Tetrabenazine(TBZ), which sometimes induces depression in humans, decreased the spontaneous locomotion in rats, and attenuated the content of amines in several regions in the rat brain when intraperitoneally injected. TJS-010 was orally administered at a concentration of 750 mg/kg, and inhibited the locomotor suppression. The content of amines was not, however, altered. These results indicate that TJS-010 postsynaptically modulates the transmission or transduction. Imipramine, 5mg/kg, also enhanced locomotion in TBZ-treated rats, which was similar to the effect of TJS-010. These results suggest that TJS-010 has an antidepressive effect. TJS-010 also facilitated the hypothermia induced by subcutaneous injection of 0.1 mg/kg (+/-)-8-hydroxy-2-(di-N-propylamino)tetralin (8-OH-DPAT), which is known to be mediated by serotonin-1A receptors. The hypothermia in the rats via an activation of serotonin-1A receptors is often observed with anxiolytic drugs. These results may raise the possibility that TJS-010 has an anxiolytic property. TJS-010 may serve as a useful drug for the treatment of those who suffer from depressive and anxiety disorders.

[Studies on lithium potentiation of antidepressant treatment].

The effects of chronic administration of clomipramine or citalopram (CMI or CIT, 20 mg/kg i.p. daily for 19 days) with/without short-term administration of lithium (Li, 2 mEq/kg i.p. daily for 5 days) on the concentration of monoamines and their metabolites and serotonergic receptors were studied in the rat cerebral cortex. Li or CMI by itself had no effects on the concentration of monoamines and their metabolites, but a combination of CMI and Li increased that of 5-HIAA. CIT alone increased that of 5-HIAA, and a combination of CIT and Li increased that of 5-HIAA more than CIT alone. There were no changes in 5-HT or 5-HIAA after acute administration of CMI or CIT with/without Li. For the serotonergic receptors, [3H] 8-OH-DPAT and [3H] paroxetine binding did not change in any of the treatments. CMI alone or a combination of CMI and Li reduced [3H] ketanserin binding, but Li did not potentiate this effect. It is speculated that the therapeutic action of Li when added to tricyclic antidepressants in the treatment of refractory depression may partly have its basis in potentiation of effects on the activation of presynaptic serotonergic system.

[Effect of long-term feeding with tryptophan-free diet on the circadian rhythm in rats].

Effects of long-term feeding with tryptophan (TRP)-free diet on the free running periods of wheel-running rhythm and the central serotonergic neurotransmission were examined in male blinded rats. Long-term feeding with TRP-free diet did not change the periods of wheel-running rhythm calculated from chi 2 periodogram but disordered its pattern, which seemed to be due to masking or entrainment effects. On the other hand, long-term TRP-free diet decreased the concentrations of TRP, 5-hydroxytryptamine (5-HT) and 5-hydroxyindoleacetic acid (5-HIAA) in all brain regions tested; frontal cortex, hippocampus, thalamus, hypothalamus and pons. The density of 5-HT1A receptor (3H-8-OH-DPAT) binding was significantly decreased in only frontal cortex, while no significant change was observed in the density of 5-HT2 receptor (3H-ketanserin) binding in all regions. Although the mechanism of down-regulation of 5-HT1A receptor in frontal cortex is obscure, it was confirmed that TRP-free diet decreased central 5-HT synthesis and 5-HT neurotransmission. This dysfunction of 5-HT neurotransmission by TRP-free diet is suggested to make the circadian rhythm pacemaker susceptible to subtle environmental factors by lowering its intensity.