Prediction of antidepressant response to venlafaxine by a combination of early response assessment and therapeutic drug monitoring.

INTRODUCTION: Early assessment of a therapeutic response is a central goal in antidepressant treatment. The present study examined the potential for therapeutic drug monitoring and symptom rating to predict venlafaxine treatment efficacy (measured by overall patient response and remission). METHODS: 88 patients were uptitrated homogenously to 225 mg/day venlafaxine. Serum concentrations of venlafaxine (VEN) and its active metabolite O-desmethylvenlafaxine (ODV) were measured at week 2. Continuous psychopathometric ratings were measured for up to 6 weeks by independent study raters. RESULTS: An early improvement was significantly more common in venlafaxine responders than non-responders (χ(2); p=0.007). While ODV serum levels were significantly higher in responders (t test; p=0.006), VEN serum levels, sum level of VEN+ODV and the ratio of ODV/VEN levels were not. Moreover, patients who showed an early response combined with an ODV serum level above the median of 222 ng/mL were significantly more likely to achieve full response (binary logistic model; p<0.01). Sensitivity (84% for early response) and specificity (81% for combination of early response and therapeutic drug monitoring) were sufficient to qualify as a reasonable screening instrument. CONCLUSION: Our results indicate that early improvement and ODV serum concentration are predictive of therapeutic outcome and can thus be used to guide use of the antidepressant venlafaxine.

[Assessment of possible drug-drug interactions in psychopharmacotherapy after hospital discharge using an interactive database]. / Datenbankgestützte Prüfung von möglichen Psychopharmakainteraktionen nach Entlassung aus stationärem Aufenthalt.

INTRODUCTION: Psychiatry is confronted with increasing requirements in quality management, guidelines and an increasing proportion of elderly, chronic multimorbid patients with psychiatric disorders. The latter give rise to polypharmacy which may lead to drug-drug interactions. Assessment of drug interactions is more and more difficult as the total number of drugs taken increases. In the present study hospital discharge medication was analysed semiautomatically for possible drug-drug interactions. METHODS: In-hospital cases were randomly selected. Discharge medication was analysed using PsiacOnline, a large web-based database for drug interactions. RESULTS: The selection yielded 342 cases from 213 patients (mean age 46.3 years, 53 % females). 86 patients had one psychiatric diagnosis; the other patients had at least two or more diagnoses. The discharge prescription was analysed for 55 different psychotropic drugs from 4 large drug groups (18 antidepressants; 17 antipsychotic drugs; 5 mood stabilisers/epileptic drugs and 13 different hypnotic/anxiolytic drugs). Antipsychotic drugs were the most frequent drugs (n = 334); followed by antidepressants (n = 312) and mood stabilizers (n = 112). 47 patients (13.7 %) were discharged with monotherapy. Mean drug number was 2.7. PsiacOnline revealed 535 hits: 126 (23.6 %) combinations were non-critical, 86 (16.1 %) combinations were critical based on pharmacological properties of the drugs; 232 (43.4 %) combinations were critical according to in vitro studies or animal experiments; critical drug combinations in high-risk patients: 67 × (12.5 %); combinations with reported risks for side effects due to interaction: 17 × (3.2 %) and combinations with documented risks for severe drug interactions: 7 × (1.3 %). CONCLUSION: Although the majority of drug combinations was considered not critical, approximately 3 % of cases had an increased risk for adverse drug actions and a further 1.3 % cases with a severe risk gave evidence that integration of an IT-based pharmacological expert system in a computerised physician order entry (CPOE) should be considered. Suggested beneficial effects need to be shown by an appropriately-designed clinical study.

[Therapeutic drug monitoring in epileptology and psychiatry]. / "Therapeutic drug monitoring" in Epileptologie und Psychiatrie.

Experts from epileptology and psychiatry reviewed the current significance of therapeutic drug monitoring (TDM) of antiepileptic drugs and psychiatric drugs in a workshop at Bethel Epilepsy Centre in December 2005. TDM has been essential in epileptology for about 30 years, and it is also increasingly important in psychiatry, in which consensus recommendations were published recently. With regard to cost-cutting in the health system, there are discussions about the financial effect of TDM and outsourcing it to bigger laboratories. In psychiatry it has however been shown that sensibly used TDM may lead to reduced costs. Many issues in TDM require the knowledge and experience of specialised laboratories. The use of TDM data for scientific purposes was discussed at the workshop as well.

Therapeutic drug monitoring of antidepressants--clinical aspects.

Therapeutic Drug Monitoring (TDM) is a tool to optimise antidepressant pharmacotherapy improving efficacy and avoiding side effects. The Arbeitsgemeinschaft für Neuropsychopharmakologie und Pharmakopsychiatrie (AGNP)-TDM group has worked out consensus guidelines to make progress in the use of TDM which in spite of its obvious advantages, is far from optimal in everyday clinical practice. Research-based levels of recommendation were defined with regard to routine monitoring of plasma concentrations for dose titration. Main indications of TDM compromise control of compliance, lack of clinical response or adverse effects at recommended doses, drug interactions, pharmacovigilance programs, presence of a genetic predisposition particularity concerning the drug metabolism, children, adolescents and elderly patients. Therapeutic ranges of plasma concentrations that are considered to be optimal for treatment are proposed, implications on pharmacoeconomics aspects are discussed. The need to improve the implementation of TDM in routine patient care is emphasized.