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.Arch.Gen.Psychiatry, 56: 821–827.8.Mavissakalian M., Perel J.(2002) Duration of imipramine therapy and relapse in panic disorder with agoraphobia.J.Clin.Psychopharmacol., 22: 294–299.9.Mavissakalian M., Perel J.M, de Groot C.(1993) Imipramine treatment of panic disorder with agoraphobia: the second time around.J.Psychiatr.Res., 27: 61–68.3.12Pharmacotherapy of Phobias: A Long-Term EndeavourMarcio Versiani1A number of medications have proven efficacy in the treatment of socialphobia (or social anxiety disorder).Selective serotonin reuptake inhibitors (SSRIs), particularly paroxetine and sertraline, emerged as the first-linetreatment, given the amount of evidence related to efficacy and their benign tolerability and safety profiles.Evidence for the efficacy of benzodiazepines (clonazepam and broma-zepam) in the treatment of social phobia has also been shown.Their use inlarge samples of patients has been problematic, though, due to dependence,extreme difficulty to withdraw the medication after medium- or long-termtreatment, sedation, cognitive disturbance and behavioural disinhibition[1].Benzodiazepines should, therefore, be reserved for refractory cases, as third-line treatment and employed with caution, for short periods of time.Many well-controlled studies have demonstrated the efficacy of classicalmonoamine oxidase inhibitors (MAOIs) such as phenelzine, and one openlong-term study has pointed to the high efficacy of tranylcypromine in thetreatment of social phobia.Extreme caution should surround the use ofclassical MAOIs in clinical practice, though.The risk of hypertensive crises, potentially fatal or leading to irreversible and serious neurological sequelae, induced by drug or food interactions, but also ‘‘endogenous’’ (without anyapparent reason), renders these drugs too dangerous for such a condition as social phobia, with very rare exceptions, such as an extremely severe case, completely refractory to other treatments and under close monitoring [1].Social phobia is a chronic, unremitting condition that commences early,in childhood or initial adolescence.When the clinician sees a case, he will be dealing with an illness history of decades.The chronicity coupled withingrained avoidance behaviours probably underlies the partial response1 Department of Psychiatry, Federal University of Rio de Janeiro, R.Visconde de Piraja 407 s.805, Rio de Janeiro, 22410-003, BrazilPHARMACOTHERAPY OF PHOBIAS: COMMENTARIES _____________________________ 171seen in most patients in short-term clinical trials with drugs.The meanreduction in the total score of the Liebowitz Social Anxiety Scale (LSAS) in 8- to 12-week drug trials has been almost invariably inferior to 50%,meaning that a lot remains for remission to be achieved [2].Long-term pharmacotherapy trials in social phobia, although still few innumber, do provide evidence for greater degrees of improvement as thedrug treatment progresses over months.Sustained remission, measured byvery low total scores of the LSAS, is seen after one year or more ofcontinuous drug treatment in approximately half of the initially treatedpatients, in open studies [1,3,4].These observations need confirmation inlong-term placebo-controlled drug studies.Another indication of the need for long-term pharmacotherapy in socialphobia stems from the high relapse rate seen after 6 months or even 2 years of treatment [4,5].The long-term pharmacotherapy of social phobia poses problems forpatients that should be dealt with by their doctors.The symptoms of social phobia are not continuous like those of, e.g., major depression.Patientswhen not exposed to phobic situations or free from anticipatory anxietymay be quite asymptomatic, ‘‘normal’’ indeed, and may become moresensitive to the unwanted effects of medications, such as weight gain,sexual inhibition or gastrointestinal disturbances.One may try to reduce the maintenance dose of the drug for better tolerability, but if signs of relapse appear the effective dose should be reinstated [1].The absolute majority of drug trials for the treatment of agoraphobia haveincluded patients with panic disorder (with or without agoraphobia).Also,in most of these studies the primary variable for the assessment of efficacy has been the frequency of panic attacks, thought to be the major target for drug effects.The rationale is that by blocking panic attacks the drug results in the amelioration of agoraphobia, as a consequence or in a secondaryway [6].The relationship between panic attacks and the development ofagoraphobia does not seem to be that simple, though, and studies haveyielded conflicting findings [7,8].Some patients develop agoraphobiaearly, after few panic attacks, others later after many attacks and others do not develop agoraphobia at all.Other factors, e.g.comorbidity andpersonality features, seem to be important in the development ofagoraphobia.In a few studies, such as one with paroxetine [9], the drugwas effective in treating agoraphobia resistant to psychotherapy.Findingssuch as this highlight the need for pharmacotherapy studies aimed atagoraphobia per se.Agoraphobia with a history or presence of panic attacks, the conditionthat has been studied in clinical trials, is a chronic disorder with acontinuous course in the majority of cases.Although scarce, long-term172 __________________________________________________________________________________________ PHOBIAStreatment studies with drugs support the need for chronic treatment formore than a year for relapse prevention [6,8].REFERENCES1.Versiani M.(submitted) The long-term drug treatment and follow-up of over250 patients with social anxiety disorder (social phobia) over 10 years.2.Versiani M.(2000) A review of 19 double-blind placebo-controlled studies in social anxiety disorder (social phobia).World J.Biol.Psychiatry, 1: 27–33.3.Liebowitz M.R.(1999) Update on the diagnosis and treatment of social anxiety disorder.J.Clin.Psychiatry, 60 (Suppl.18): 22–26.4.Versiani M., Amrein R., Montgomery S.A.(1997) Social phobia: long-termtreatment outcome and prediction of response—a moclobemide study.Int.Clin.Psychopharmacol., 12: 239–254.5.Stein D.J., Versiani M., Hair T., Kumar R.(2002) Efficacy of paroxetine for relapse prevention in social anxiety disorder: a 24-week study.Arch.Gen.Psychiatry, 59: 1111–1118.6.Keller M.B.(2002) Raising the expectations of long-term treatment strategies in anxiety disorders.Psychopharmacol.Bull., 36 (Suppl.2): 166–174.7.Katerndahl D.A.(2000) Predictors of the development of phobic avoidance.J.Clin.Psychiatry, 61: 618–623.8.Katschnig H., Amering M.(1998) The long-term course of panic disorder and its predictors.J.Clin.Psychopharmacol., 18 (Suppl.2): 6S–11S.9.Kampman M., Keijsers G.P., Hoogduin C.A., Hendriks G.J.(2002) A random-ized, double-blind, placebo-controlled study of the effects of adjunctiveparoxetine in panic disorder patients unsuccessfully treated with cognitive-behavioral therapy alone.J.Clin.Psychiatry, 63: 772–777.3
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