After another month, Mr. I self-discontinues the mirtazapine. Though he tries to participate in social situations, his anxiety has worsened. He goes to a country music club once a week but is afraid to ask anyone to dance.
Should you focus on Mr. I’s depression rather than his social phobia? If so, how do you change his treatment?
Drs. Yu’s, Gordon’s, and Maguire’s observations
The severity of Mr. I’s social phobia may be causing his depression. Both trials of bupropion SR and mirtazapine have been adequate for his depression but have not alleviated his social phobia.
Medications that affect gamma-aminobutyric acid (GABA) levels, specifically benzodiazepines, have not been tried. Benzodiazepines provide rapid relief with little risk in short-term treatment, but dependence/withdrawal risks increase greatly when given more than 4 to 6 months.8 Because of Mr. I’s chronic anxiety in social phobia and his history of alcoholism, benzodiazepines are not recommended.
The novel compound tiagabine has been shown to increase GABA in the synaptic cleft.12 GABA increases chloride conduction through its ligand-gated channels, creating a potential antianxiety effect similar to that produced by benzodiazepines.8,13,14 GAT-1, the predominant transporter, removes excess GABA.
Just as SSRIs inhibit serotonin reuptake and allow the neurotransmitter to act on its receptors to alleviate depression and anxiety, so does tiagabine inhibit GAT-1. Theoretically, tiagabine may relieve anxiety by increasing synaptic concentrations of GABA.
Tiagabine also has been shown to be well-tolerated without a known abuse or dependence potential.12 Possible adverse effects include impaired concentration, somnolence, fatigue, nausea, and dizziness. To avoid adverse effects, slow titration (about 4 mg per week) is recommended.
Changing treatment: Looking up
Tiagabine, 4 mg at bedtime, is added to help with Mr. I’s anxiety; he is instructed to increase the dosage by 4 mg every 5 days in divided doses. He began to sense improvement during the second week, at 4 mg bid, and 2 weeks later his anxiety has been greatly reduced. He can now sit quietly with his co-workers during coffee breaks and has begun training a co-worker, which he never dared to attempt before. At this point, he was tolerating tiagabine at 8 mg bid.
One month later, tiagabine is increased to 16 mg bid. Mr. I has noticed mild dizziness with each dosage increase, but each time it subsided within a day. He has been maintained on 16 mg bid.
Saying that his anxiety is now well-controlled, Mr. I enjoys at least one dance each week at the country music club he frequents. One week later, he led an Alcoholics Anonymous meeting—while looking up to his audience for the first time. He continues these activities and his therapy sessions, which are geared toward developing stronger skills to minimize his anxiety. He is considering lowering his medication dosages (though he is wary of a possible relapse) and furthering his therapy.
Related resources
- Anxiety Disorders Association of America www.adaa.org
- National Institute of Mental Health: Phobias from NLM’s MEDLINEplus http://www.nlm.nih.gov/medlineplus/phobias.html
Author affiliations
Dr. Yu is a fellow in child and adolescent psychiatry, Dr. Gordon is a resident physician; and Dr. Maguire is assistant dean for continuing medical education, director of resident training, and associate clinical professor, department of psychiatry, University of California, Irvine.
Drug brand names
- Bupropion • Wellbutrin
- Buspirone • BuSpar
- Mirtazapine • Remeron
- Phenelzine • Nardil
- Tiagabine • Gabitril
- Venlafaxine • Effexor
Disclosure
Dr. Yu reports that he serves on the speaker’s bureau of Cephalon Inc., Novartis Pharmaceuticals Corp., and Pfizer Inc., and receives research/grant support from and serves as a consultant to Eli Lilly and Co.
Dr. Gordon reports no financial relationship with any company whose products are mentioned in this article, or with manufacturers of competing products.
Dr. Maguire reports that he receives research/grant support from, serves as a consultant to, and is on the speaker’s bureau of Eli Lilly and Co., is on the speaker’s bureau of Pfizer Inc., and receives research/grant support from Forest Laboratories and GlaxoSmithKline.