87Personalized medicine -the adaptation of therapies based on an individual's genetic and molecular profile -is one of the most promising aspects of modern medicine. The identification of the relation between genotype and drug response, including both the therapeutic effect and side effect profile, is expected to deeply affect medical practice. In this paper, we review the current knowledge about the genes related to antidepressant treatment response and provide methodologic proposals for future studies. We have mainly focused on genes associated with pharmacodynamics, for which a list of promising genes has been identified despite some inconsistency across studies. We have also synthesized the main results for pharmacokinetic genes, although so far they seem less relevant than those for pharmaco dynamic genes. We discuss possible reasons for these inconsistent findings and propose new study designs.

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Despite the well-known efficacy of selective serotonin reuptake inhibitors (SSRIs) and serotonin-norepinephrine reuptake inhibitors (SNRIs) in the treatment of major depressive disorder, there is a lack of indications for each drug in different groups of patients. The aim of this study is to investigate the possible role of clinical sociodemographic factors as moderators of clinical response to venlafaxine (SNRI) and sertraline (SSRI). Research was performed on Medline and EMBASE for randomized control trials in English focused on sertraline and venlafaxine in the treatment of major depressive disorder and 59 studies were included. Clinical efficacy of each treatment was assessed on the basis of Hamilton Depressive Rating Scale and Montgomery-Asberg Depression Rating Scale. A metaregression analysis was performed to evaluate the role of clinical and sociodemographic factors as moderators of outcome, calculating the effect of each variable with the random-effects method. Gender, ethnicity and duration of depressive episode could have a role in prediction of clinical response to both antidepressants. Venlafaxine seems to have better effects in females and in Caucasian patients. Sertraline seems to be more efficacious in the treatment of females. Both drugs were more efficacious in patients who suffered a shorter episode of illness. Our results could represent an interesting point of view in the perspective of choosing the most suitable therapy based on clinical and social features for each patient. Metaregression is a retrospective analysis, based on the cumulative results of previous studies, so the lack of original data could represent the main limitation in this report and in the interpretation of the results obtained.

In previous subanalysis and metaregression analysis, paroxetine failed to show clear differences in terms of efficacy across clinical subgroups. Thus, nowadays the pharmacokinetic and pharmacodynamic properties of the molecule are fundamental to guiding its prescription, both for efficacy and tolerability issues, for example, it can have a high impact on sexual function and weight should also be considered at the beginning of treatment. Since prescription is still based mainly on its side-effect profile, newer and more accurate directions for an individualized prescription are needed.

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A 71-year-old man developed coma with severe respiratory failure, hypotension, and tachycardia induced by the intentional ingestion of quetiapine fumarate extended release (XR) 20 g. At the time, he had been treated for bipolar depression with venlafaxine 75 mg/day, lamotrigine 100 mg/day, pregabalin 75 mg/day, and quetiapine XR 400 mg/day for approximately 1 year. Comorbidities were hypertension treated with metoprolol, diabetes mellitus type 2 treated with metformin, and benign prostatic hyperplasia treated with silodosin. In the emergency room, about 4 h after ingestion of quetiapine fumarate XR, the presenting symptomatology was characterized by coma (Glasgow Coma Scale score 3), hypotension (blood pressure [BP] 90/60 mmHg), tachycardia (electrocardiogram [ECG] showed sinus tachycardia with heart rate 120 beats per minute and a QTc of 499 ms). A gastric lavage was performed and activated charcoal 50 g and magnesium sulfate 30 g was administered. About 6 h after ingestion, he developed marked desaturation and underwent mechanical ventilation; 13 h after ingestion, a severe hypotensive episode followed (BP 70/40), which was treated with an infusion of ringer lactate 500 cc. On the 3rd day after intentional overdose, an episode of agitation occurred; 4 days after ingestion, the quetiapine plasma level was found to be 42 ng/ml (within therapeutic range). At 5 days after ingestion, the patient developed septicemia caused by staphylococci (probably originating from the central vein catheter), which was treated with antibiotic therapy. On days 10 and 18 after the suicide attempt, two episodes of paroxysmal supraventricular tachycardia (PSVT) occurred and were successfully treated with intravenous adenosine triphosphate. The patient recovered completely without residual symptoms. In line with literature data, in this case report, symptoms of quetiapine overdose were tachycardia, agitation, hypotension, QT interval prolongation, and coma. A causal relationship between PSVT and quetiapine intoxication seems quite unlikely due to the drug level.

Patients with relatively mild illness severity might be more susceptible to early worsening of symptoms when switched to aripiprazole. However, the limitations of the present study, including a small sample size, absence of a control group designed to control for nonspecific factors such as regression to the mean, and implementation of a switching strategy that included only aripiprazole, mean the present findings should be considered with caution and further research is needed.

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