Influence of Genetic Polymorphisms and Concomitant Anxiolytic Doses on Antidepressant Maintenance Doses in Japanese Patients with Depression

Abstract

To prevent recurrent depression, patients should ideally continue treatment for >6 months with the antidepressant dose that effectively suppressed acute depressive symptoms. However, there are inter-individual differences in the antidepressant doses required to achieve response and maintenance. Therefore, this study was conducted to examine the role of clinical features, including genetic polymorphisms, on the antidepressant dose required for maintenance therapy in 82 Japanese patients with depression. We calculated the antidepressant dose using the imipramine equivalent scale and the dose of concomitant anxiolytics and hypnotics using the diazepam equivalent scale. The 82 participants were classified into two groups based on the median imipramine equivalent dose, and we examined the influence of patient characteristics and the presence of genetic polymorphisms of brain-derived neurotropic factor (BDNF; rs6265) and cyclic adenosine monophosphate responsive element-binding protein 1 (CREB1; rs2253306, rs4675690, rs769963) on the antidepressant maintenance dose. Using a multivariate logistic regression analysis, we found that the concomitant diazepam equivalent dose and presence of the CREB1 rs4675690 polymorphism were significantly associated with the antidepressant maintenance dose. We concluded that these factors influenced the antidepressant dose in maintenance therapy among Japanese patients with depression. However, further research is required in large cohorts.Key words antidepressant; maintenance dose; depressive disorder; polymorphism; brain-derived neurotrophic factor; cyclic AMP responsive element binding protein 1 Depressive disorder is a common psychiatric disorder, with approximately 350 million people being affected worldwide. 1)Moreover, it is associated with a high rate of recurrence and chronicity, with 12-35% of all cases becoming chronic and 13.2% experiencing recurrence within 5 years.2-5) When starting antidepressant therapy, the dose of antidepressant is low and is slowly increased, and careful attention is paid to the development of anxiety, agitation, panic attacks, insomnia, irritability, hostility, aggressiveness, impulsivity, akathisia, hypomania, and mania, the so-called "activation syndrome." The target dose is the lowest dose that adequately suppresses depressive symptoms with tolerable side effects. After achieving remission, the therapeutic dose acutely required is continued as maintenance therapy for >6 months to prevent recurrence. 6,7)Several reports suggest that when an antidepressant is ineffective in suppressing depressive symptoms, combination therapy with another antidepressant or anxiolytic or hypnotic drugs is more effective than increasing the dose of the preexisting antidepressant. [8][9][10] In studies on Japanese patients with depression, 23.4-35.9% of cases were treated with antidepressant combination therapy and 60.3-73.0% were treated with concomitant anxiolytic or hypnotic drugs. In addition, it is known that inter-individual differences exist in the daily dosing ...

Correlation between variants of the CREB1 and GRM7 genes and risk of depression

“…Daniela et al reported that CREB1 plays an antidepressant role by regulating the expression of certain genes [ 10 ]. Additionally, studies have shown that CREB1 plays a role in the effects of antipsychotics and mood stabilizers [ 11 – 13 ]. Several standard antidepressant treatment agents, including norepinephrine reuptake inhibitors and selective serotonin reuptake inhibitors, were found to result in elevated CREB1 activity in the hippocampus [ 9 , 14 , 15 ].…”