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Modafinil for Social Phobia and Amphetamine Dependence

To the Editor: The treatment of psychiatric disorders in individuals with an active substance use problem is a challenge for the practicing clinician (1).

Ms. A was a 45-year-old Caucasian woman who came to our outpatient clinic for treatment of social phobia and comorbid amphetamine dependence. Her symptoms started during her early 20s. She described episodes of overwhelming anxiety, especially when she needed to present projects to her teachers. She had a partial response to fluoxetine. A friend introduced her to amphetamines; she started using them on a regular basis at age 27. She reported some relief of her anxiety, but 1 year later she met criteria for amphetamine dependence. She dropped out of school, became homeless, and was incarcerated several times for drug possession.

Her health care providers recommended that she enroll in drug rehabilitation before any further pharmacological treatment could be pursued. At one point, Ms. A was given a trial of methylphenidate and dextroamphetamine. She misused these prescription drugs. She had difficulties working with health care providers because of her explosiveness, overwhelming anxiety, agitation, and depression. She refused to take any medication that caused her to gain weight. She achieved no benefit from trials of lithium, anticonvulsants, venlafaxine, bupropion, selective serotonin reuptake inhibitors, and atypical antipsychotics. We started modafinil treatment, up to 200 mg b.i.d. At this point, she was also taking fluoxetine, 40 mg/day. She reported that her craving for amphetamines diminished, and her anxiety and depression improved. She did not spend most of her time looking for the amphetamines in the street and was able to apply for a regular job. She did not report the same "high" with modafinil that she experienced with amphetamines. Ms. A now works part-time and recently returned to school.

Modafinil is a new stimulant approved for the treatment of narcolepsy. Its mechanism of action is unknown (2). Studies (3) have indicated that it does not have the anxiogenic properties of dextroamphetamines. Recent studies (4) have raised the hypothesis of a possible link between dopamine dysfunction and social phobia.

In 1997, San Diego reported the highest mortality rate associated with methamphetamine overdose; it continues to be the most common primary drug of abuse (5). This case illustrates the increasing need for double-blind placebo-controlled clinical trials in the dually diagnosed population, specifically in individuals actively using stimulants.

References

1. Marlatt GA, Tucker JA, Donovan DM, Vuchinich RE: Help-seeking by substance abusers: the role of harm reduction and behavioral-economic approaches to facilitate treatment entry and retention. NIDA Res Monogr 1997; 165:44-84[Medline]
2. Engber TM, Dennis SA, Jones BE, Miller MS, Contreras PC: Brain regional substrates for the actions of the novel wake-promoting agent modafinil in the rat: comparison with amphetamine. Neuroscience 1998; 87:905-911[CrossRef][Medline]
3. Simon P, Panissaud C, Costentin J: The stimulant effect of modafinil on wakefulness is not associated with an increase in anxiety in mice: a comparison with dexamphetamine. Psychopharmacology (Berl) 1994; 114:597-600[CrossRef][Medline]
4. Schneier FR, Liebowitz MR, Abi-Dargham A, Zea-Ponce Y, Lin S-H, Laruelle M: Low dopamine D₂ receptor binding potential in social phobia. Am J Psychiatry 2000; 157:457-459[Abstract/Free Full Text]
5. Community Epidemiology Work Group: Epidemiologic Trends in Drug Abuse, Highlights and Executive Summary, vol 1. Bethesda, Md, National Institute on Drug Abuse, 1998, pp 59-66

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