Confirmation of the neurophysiologically predicted therapeutic effects of trazodone on its target symptoms depression, anxiety and insomnia by postmarketing clinical studies with a controlled-release formulation in depressed outpatients.
Early human pharmaco-EEG and subsequent sleep laboratory studies identified trazodone, a 5-HT(2) antagonist and 5-HT reuptake inhibitor (SARI), as an antidepressant with therapeutic effects on its target symptoms depressed mood, anxiety and insomnia. On the occasion of the introduction of a controlled-release (CR) formulation (Trittico 150 mg retard, marketed in Austria by CSC Pharmaceuticals Handels GmbH, Vienna, Austria) in Austria in July 2000, a multi-center, open, clinical post-marketing study on the therapeutic effects, safety and target symptoms of trazodone CR in depression was carried out at 80 offices of Austrian neuropsychiatrists. 549 outpatients (63% females) of all age groups suffering from five different subtypes of depression were enrolled in the study. After a 2-week fixed dose-titration regimen up to 150 mg and a 4-week adjustment period to the optimum dose, 66% of the patients remained on 150 mg, 20% increased the dose and 11% decreased it. Only 3.7% discontinued treatment. Rating by the neuropsychiatrists based on the Clinical Global Impression showed very much to much improvement in 78.3% of the patients, and no change or a deterioration in only 3.6%. In the Hamilton Depression Scale (HAMD) a statistically significant improvement from a baseline score of 21 to a score of 14 after 2 weeks was found, and a normalization to a score of 8 after 6 weeks. Therapeutic effects were similar in the five groups suffering from different subtypes of depression and in patients with and without comedication. Self-rating by the patients based on the Zung Self-Rating Depression Scale (SDS) and Zung Self-Rating Anxiety Scale (SAS) also showed a significant improvement in the 2nd and 6th week of therapy. Evaluation of the target symptoms of trazodone by ranking the most improved symptoms identified insomnia as the most improved psychopathological item in all three scales. While in the observer ratings also suicidal tendencies and weight loss were found much improved, in the self-rated Zung SDS sadness and loss of drive came second and third in the improvement ranking, in the self-rated Zung SAS anxiety and the feeling of falling apart. Tolerability was very good. In the 2nd week only 16.9% and in the 6th week only 7.6% of the patients reported side effects, mostly characterized by tiredness and rarely by nausea and vertigo. The present clinical study is in agreement with previous studies identifying trazodone as a safe and effective antidepressant, specifically regarding its target symptoms insomnia, depression and anxiety. It also confirms our own early predictions based on neurophysiological investigations concerning the mode of action of the drug.
Saletu-Zyhlarz
Gerda Maria
GM
Department of Psychiatry, University of Vienna, Vienna, Austria.
Anderer
Peter
P
Arnold
Oliver
O
Saletu
Bernd
B
D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D018687:Antidepressive Agents, Second-Generation / Q000627:therapeutic use*; D001007:Anxiety / Q000188:drug therapy*; D001714:Bipolar Disorder / Q000145:classification / Q000150:complications / Q000188:drug therapy*; D016009:Chi-Square Distribution; D003692:Delayed-Action Preparations / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009483:Neuropsychological Tests; D010045:Outpatients; D011237:Predictive Value of Tests; D011358:Product Surveillance, Postmarketing; D011569:Psychiatric Status Rating Scales; D007319:Sleep Initiation and Maintenance Disorders / Q000188:drug therapy* / Q000209:etiology; D013405:Suicide / Q000523:psychology; D013997:Time Factors; D014196:Trazodone / Q000627:therapeutic use*; D015431:Weight Loss / Q000187:drug effects
D018687:Antidepressive Agents, Second-Generation; D003692:Delayed-Action Preparations; D014196:Trazodone