مقایسه دو سو کور 30 و 60 میلی گرم روزانه ترانیل سیپرومین در بیماران مبتلا به اختلال پانیک همزمان با اختلال اضطراب اجتماعی

Our objective was to explore the dose–response relationship in patients with panic disorder and social anxiety disorder comorbidity (DSM-IV). After 1 week of no-drug washout, 36 such patients were assigned to a double-blind controlled comparison of the effects of 30 mg and 60 mg of tranylcypromine, and were followed up for 12 weeks. The main instrument used to measure the number of panic attacks was the Sheehan Panic and Anticipatory Anxiety Scale. The primary outcome measure for social anxiety disorder symptoms was the mean change from baseline in the Liebowitz Social Anxiety Scale (LSAS). After 12 weeks of treatment, panic attacks were reduced 69.6% from baseline in the 30-mg group (n = 19) compared with a 74.8% reduction in the 60-mg group (n = 17). Twelve patients (70.6%) of the higher dose group and 14 patients (68.4%) of the lower dose were completely free of panic attacks. There was no difference in efficacy between the tranylcypromine groups in the panic disorder symptoms. The 60-mg dose was more efficacious as measured by the LSAS scores, showing a significant difference in relation to the lower group. Mean change from baseline in LSAS total score (mean ± SD) for 30-mg group was − 17.9 ± 14.7 and for the 60-mg group was − 35.0 ± 14.8. The social anxiety symptom scale showed a two-fold greater change with the 60-mg dose, and the 30-mg dose group could be considered the equivalent of a placebo control group. Tranylcypromine – 60 mg daily – was found effective in the treatment of panic disorder and social anxiety disorder comorbidity.

The concept of comorbidity has clinical and theoretical implications (Frances et al., 1990). Situational panic attacks are common in social anxiety disorder (Liebowitz et al., 1985), and non-situational panic attacks occur frequently in anxiety disorders as well as in panic disorder (Liebowitz et al., 1985 and Frances et al., 1990). The diagnostic dilemma presented by patients who exhibit both panic disorder and agoraphobia and who avoid certain performance or social situations has been addressed by Liebowitz et al. (1985). The term “primary social anxiety disorder” was suggested for those patients who fear scrutiny or evaluation by others and whose anxiety is confined to social situations or anticipation. “Secondary social anxiety disorder” would apply to those patients who have panic attacks in nonsocial situations and fear/avoid situations where an exit is not available. Occasionally, cases of anxiety disorder comorbidity are described as a clinical curiosity (Goldstein, 1987). Goldstein (1987) presented three cases in which the DSM-III classificatory distinctions are blurred, and the course of the illness seems to involve temporary overlapping manifestations of panic attacks, social anxiety disorder and agoraphobia. The association between lifetime anxiety disorders and personality disorders among adults in the community was explored by Goodwin and Hamilton (2003). Their data were drawn from the National Comorbidity Survey (n = 5877), a representative community sample of adults aged 15–54 in the 48 US states. Out of the 3.3% of adults with antisocial personality disorder (ASPD), over half (54.33%) had a comorbid anxiety disorder (lifetime). Similarly, 42.31% of adults with a history of conduct disorder (CD) (9.4%) who did not meet criteria for ASPD had a lifetime anxiety disorder. Social anxiety disorder and post-traumatic stress disorder were associated with significantly increased odds of ASPD. The comorbidity of anxiety disorders and ASPD was associated with significantly higher odds of major depression, substance use disorders, and suicide ideation and attempt compared with odds among those without both disorders. These data provide initial evidence of an association between post-traumatic stress disorder and social anxiety disorder, and an increased likelihood of ASPD among adults in the community, after adjustment for comorbid affective and substance use disorders. Adults with ASPD and comorbid anxiety had significantly higher levels of comorbid major depression, alcohol dependence, and substance dependence and substantially higher rates of lifetime suicidal ideation and suicide attempts compared with adults with ASPD or anxiety disorders alone or with neither disorder. Over the last two decades the combination of selective serotonin reuptake inhibitors (SSRIs) with cognitive-behavioural therapy (CBT) has been considered an efficacious option for the treatment of anxiety disorders (Roy-Byrne et al., 2006). The clear efficacy and increased tolerability of the SSRIs over previous treatments (tricyclics and monoamine oxidase inhibitors — MAOI) have led to the widespread conclusion of their being the first-line choice in all these disorders (Roy-Byrne et al., 2006). In a clinical setting the treatment of choice depends on a number of issues, including adverse effects, efficacy, and the presence of concomitant syndromes. It is crucial to provide a risk-benefit assessment for each patient, and the treatment choice should be based on individualized assessment. From this point of view, there is still a place for older drugs such as the MAOIs in certain cases, and they should be studied in special populations. Arnot (1960) was the first to describe the anxiolytic effect of a MAOI. Sheehan et al. (1980) showed that phenelzine was superior to imipramine in relation to several panic disorder measures, including reduction of disability, and this finding renewed interest in this class of drug for treating panic disorder. Since then, MAOIs have been shown to be efficacious in social anxiety disorder (Deltito and Perugi, 1986, Liebowitz et al., 1986, Versiani et al., 1988, Liebowitz et al., 1988 and Versiani et al., 1992) and panic disorder or comparable disorders (Sargant, 1969, Tyrer et al., 1973, Sheehan et al., 1980, Versiani et al., 1987 and Tyrer and Shawcross, 1988). The first double-blind study with patients with social anxiety disorder (Liebowitz et al., 1988) compared phenezine and atenolol with placebo in the treatment of 74 patients with social anxiety disorder. The average dose was 76 mg/day for phenelzine. At the end of the 16-week treatment period, about 2/3 of the patients treated with phenelzine showed a significant improvement, whereas less than 1/3 improved with atenolol and placebo. Although MAOIs are an effective antipanic agent (Sargant, 1969, Sheehan et al., 1980, Versiani et al., 1987 and Tyrer and Shawcross, 1988), they are generally used as second line agents due to their associated adverse reactions and dietary restrictions (Jann and Kurtz, 1987 and Bechelli et al., 1989). A disadvantage of the conventional irreversible MAOIs is the risk of hypertensive crises when combined with dietary tyramine (Tyrer and Shawcross, 1988 and Bechelli et al., 1989). There are no important therapeutic differences between the MAOIs, and there is growing evidence that MAOIs are somewhat more effective than tricyclic antidepressants in the treatment of anxiety disorders and when phobic anxiety is an important component of a depressive disorder (Jann and Kurtz, 1987 and Tyrer and Shawcross, 1988). Patients that present the characteristic features of both social anxiety disorder and panic disorder (Liebowitz et al., 1985) might benefit most from a treatment suited for both disorders. This study was designed to explore the dose–response relationship for tranylcypromine in patients with panic disorder (with and without agoraphobia) with social anxiety disorder comorbidity — DSM-IV. Our hypothesis is that a higher dose of tranylcypromine may be necessary to the treatment of social anxiety disorder symptoms than for panic disorder symptoms considering not only the phobic avoidance but the panic attack and the anticipatory anxiety. This different response to a lower and a higher dose may be associated with the dopaminergic system in social anxiety disorder (Ressler and Nemeroff, 2000).