Selective serotonin reuptake inhibitors are the pharmacological treatment of choice for the treatment of social anxiety disorder (SAD). The efficacy and tolerability of fixed doses of escitalopram were compared to those of placebo in the long-term treatment of generalised SAD, using paroxetine as an active reference. Patients with a DSM-IV diagnosis of SAD between 18-65 years of age were randomised to 24 weeks of double-blind treatment with placebo (n = 166), 5 mg escitalopram (n = 167), 10 mg escitalopram (n = 167), 20 mg escitalopram (n = 170), or 20 mg paroxetine (n = 169). Based on the primary efficacy parameter, Liebowitz Social Anxiety Scale (LSAS) total score at Week 12 (LOCF), a significantly superior therapeutic effect compared to placebo was seen for 5 and 20 mg escitalopram and for all doses for the OC analyses. Further improvement in LSAS scores was seen at Week 24 (OC and LOCF), with significant superiority over placebo for all doses of escitalopram, and 20 mg escitalopram was significantly superior to 20 mg paroxetine. Response to treatment (assessed by a Clinical Global Impression-Improvement score < or = 2) was significantly higher for all active treatments than for placebo at Week 12. Clinical relevance was supported by a significant decrease in all the Sheehan disability scores, and the good tolerability of escitalopram treatment. It is concluded that doses of 5-20 mg escitalopram are effective and well tolerated in the short- and long-term treatment of generalised SAD.

Sixty-nine depressive patients (DSM III criteria: 296.2, 296.3, 296.5, 300.4) were treated with 40 to 60 mg citalopram (CIT) daily for 4 weeks. Among them, 45 responded to treatment (improvement > 50% on the 21-item Hamilton Rating Scale for Depression [HAM-D]) and continued their treatment for another week before being released from the study. The 24 nonresponders were randomized and comedicated under double-blind conditions with lithium carbonate (Li) (2 x 400 mg/day) (CIT-Li group) or with placebo (CIT-Pl group) from days 29 to 35. For days 36 to 42, the patients of both subgroups were treated openly with Li (800 mg/day) in addition to the ongoing CIT treatment. On day 35, 6 of 10 patients responded to the CIT-Li combination, whereas 2 of 14 patients only responded to the CIT-Pl combination. This group difference reached significance (p < 0.05) on day 35 with lower HAM-D total scores in the CIT-Li group. No evidence was seen of a pharmacokinetic interaction between CIT and Li, and this combination was well tolerated. Patients were phenotyped with dextromethorphan and mephenytoin at baseline and at day 28. As evaluated at baseline, three patients (responders) were poor metabolizers of dextromethorphan and six patients (three responders and three nonresponders) of mephenytoin. On day 28, the ratio CIT/N-desmethylCIT (DCIT) in plasma was significantly higher in poor than in extensive metabolizers of mephenytoin (p = 0.0001), and there was a significant positive correlation between the metabolic ratio of dextromethorphan and the ratio DCIT/N-didesmethylCIT in plasma (p < 0.001). These findings illustrate the role of CYP2D6 and CYP2C19 in the metabolism of CIT. It can be concluded that Li addition to CIT is effective in patients not responding to CIT alone without any evidence of an accentuation or provocation of adverse events.

The present overview investigates whether different antidepressants have differing discontinuation symptoms upon treatment cessation, if these symptoms vary between depression and anxiety disorders, and with length of treatment. Data came from two comparative studies of escitalopram in major depressive disorder (MDD) (one vs. venlafaxine XR and one vs. paroxetine), two studies in social anxiety disorder (SAD) (one of which used paroxetine as the active reference), and one study in generalized anxiety disorder (GAD), using paroxetine as an active reference [total number of patients: escitalopram (n=1051); paroxetine (n=336); venlafaxine XR (n=124); placebo (n=239)]. All studies included a defined discontinuation period and used the Discontinuation Emergent Signs and Symptoms (DESS) checklist to record the number of discontinuation symptoms. All three antidepressants showed more discontinuation symptoms compared with placebo (p<0.001). Patients reported significantly fewer discontinuation symptoms with escitalopram than with paroxetine and venlafaxine XR in MDD (p<0.05). Escitalopram showed significantly fewer discontinuation symptoms than paroxetine in SAD (p<0.05) and GAD (p<0.001). For each antidepressant, no differences in discontinuation symptoms were observed between the three indications and there was no evidence for increased symptom incidence with increased length of treatment. Thus, discontinuation profiles differ between antidepressants of the same class and are broadly similar in different disorders. No evidence was seen for a higher discontinuation burden with longer treatment.

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BackgroundMajor depression is highly recurrent. Antidepressant maintenance treatment has proven efficacy against recurrent depression.AimsComparison of prophylactic efficacy of citalopram versus placebo in unipolar, recurrent depression.MethodsPatients 18–65 years of age with recurrent unipolar major depression (DSM–IV), a Montgomery–åsberg Depression Rating Scale score of ≥ 22 and two or more previous depressive episodes, one within the past 5 years, were treated openly with citalopram (20–60 mg) for 6–9 weeks and, if responding, continued for 16 weeks before being randomised to double-blind maintenance treatment with citalopram or placebo for 48–77 weeks.ResultsA total of 427 patients entered acute treatment and 269 were randomised to double-blind treatment. Time to recurrence was longer in patients taking citalopram than in patients taking placebo (P < 0.001). Prophylactic treatment was well tolerated.ConclusionsCitalopram (20, 40 and 60 mg) is effective in the prevention of depressive recurrences. Patients at risk should continue maintenance treatment at the dose necessary to resolve symptoms in the acute treatment phase.

Escitalopram has demonstrated efficacy for the acute treatment of social anxiety disorder (SAD) in two placebo-controlled trials and for long-term treatment in a relapse-prevention study. Social anxiety disorder is a heterogeneous disorder. This study questions whether this new selective serotonin reuptake inhibitor is effective across different subgroups of patients. Data from two randomised, placebo-controlled, 12-week escitalopram SAD trials were pooled. General linear models were used to determine the efficacy of escitalopram in different patient subgroups. Furthermore, a factor analysis of the primary efficacy scale, the Liebowitz Social Anxiety Scale (LSAS), was undertaken, and a determination made of whether treatment effects were similar for the different symptom dimensions. Escitalopram was effective in both younger and older patients, in male and female patients, and in patients with more and less severe social anxiety symptoms. The LSAS factor analysis showed six factors, which were differentially associated with different areas of disability. Escitalopram was significantly superior to placebo for all six symptom dimensions. The treatment effects of escitalopram were independent of gender, symptom severity and chronicity, and comorbid depressive symptoms. A six-factor model of social anxiety symptoms is supported by the distinctive association between these symptom dimensions and different areas of disability, but did not predict differential response to escitalopram.

Puffing behavior (number of puffs, puff interval, puff duration, peak pressure, latency to peak pressure, average and total puff volume) was measured in 67 dependent male and 43 dependent female smokers when they smoked two cigarettes of their habitual brand under laboratory conditions. Test-retest reliability for the two cigarettes was high, and factor analysis showed that puff shape, puff volume, and puff frequency accounted for about 50% of variation obtained with the different puffing variables. Expiratory tidal CO levels increased with the number of cigarettes smoked before the tests and with the intensity of the smoking habit, but pre- to postsmoking delta tidal CO differences were similar for smokers of all types of cigarettes (0.1 - 1.7 mg standard machine smoking nicotine yield). Volume compensation for differences of smoke yield of the cigarettes was generally more pronounced in women than in men and, additionally, it was more pronounced for cigarettes with standard smoke nicotine yield below 0.9 mg than for cigarettes with standard smoke nicotine yield above 0.9 mg for both sexes. Only for women, partial correlation procedures suggested that nicotine might be more important in determining puffing behavior than CO and condensate yield, but there were also no women smoking the strongest cigarettes (1.3 - 1.7 mg nicotine yield). For both sexes, no compensation by adjusting the number of cigarettes smoked daily was obtained. Personality ratings, pulmonary functions, and cardiovascular functions were not, or only inconsistently, correlated with puffing behavior or type of cigarette.

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