Drug Treatments

Confronted with the increasingly favorable treatment outcomes associated with cognitive behavioral packages, there are three possible reasons why pharmacological interventions might be considered. First, it could be that pharmacological interventions achieve the same outcomes as the cognitive behavioral therapy packages but at a cheaper cost (financially to the patient or in terms of therapist time), with fewer dropouts, lower relapse rates, and with fewer associated difficulties (such as side-effects). Second, it could be that pharmacological treatments may be useful adjuncts to the cognitive behavioral therapy packages. Third, it could be that pharmacological interventions are useful treatments to attempt with patients for whom a comprehensive and well-conducted cognitive behavioral therapy program has failed or to whom such a treatment is unacceptable.

Before a therapist can consider each possibility, it is necessary to evaluate the literature regarding pharmacological interventions. There are five possible pharmacological interventions, the tricyclic (antidepressants), the benzodiazepines (high and low potencies), the beta blockers, the monoamine oxidase inhibitors, and the selective serotonin re-uptake inhibitors. As with every medication there are pros, cons, and guidelines for use, but at a general level of overall efficacy it appears that the low-dose benzodiazepines and the beta blockers (i.e., propranolol) have limited efficacy.

The tricyclics and the high-potency benzodiazepines have more acceptable success rates. Holland et al. (1999) reported that the tricyclic clomipramine has a slower therapeutic onset than the benzodiazepines alprazolam and adinazolam, but that it reached the same rate of efficacy as alprazolam (both being superior to adinazolam) and had less frequent withdrawal problems. Den Boer (1998) noted that a further advantage of the tricyclics over the benzodiazepines is that the former have greater effects on comorbid depression while being similarly effective in managing anxiety and agoraphobia.

Clum (1989) estimated (when dropouts are included) that behavior therapies in general are successful with 54% of patients, tricyclics with 19%, and the high-potency benzodiazepines with 42%. The unexpectedly low outcomes for the tricyclics (Mattick et al., 1990) probably occur because studies have tended to use people with panic disorder and agoraphobia (who are more difficult to treat), whereas studies with the high-potency benzodiazepines have tended to use subjects with panic disorder alone. In a similar comparison, Michelson and Marchione (1991) concluded that cognitive behavioral therapy packages are generally successful in 74% (including dropouts) of individuals with panic disorder and agoraphobia (86% among panic disorder alone), the tricyclics in 45%, and the high-potency benzodiazepines in 51%. Once again, the treatment outcomes for the low-potency benzodiazepines and beta blockers are relatively low (13% and 8%, respectively).

Although the two reviews differ in their final estimates, the pattern of results is similar, suggesting that – of the pharmacological treatments – high-potency benzodiazepines and the tricyclics are the only interventions whose outcomes approach the success obtained with a cognitive behavioral therapy package. If the choice of pharmacological intervention were limited to these two classes of drug, it would be difficult to choose between them. On the one hand, the dropout rates for the tricyclics are higher than for the high-potency benzodiazepines (although this may reflect different sampling); but, on the other hand, the relapse rates for the high-potency benzodiazepines are probably higher. In terms of unwanted effects, the tricyclics are unpopular because of the anticholinergic side-effects, but the high-potency benzodiazepines are often avoided because of the possibility of dependence and also the negative effects upon memory.

Indeed, after demonstrating the efficacy of imipramine and (especially) alprazolam in treating panic disorder, Rickels et al. (1993b) identified a “sobering fact [that] over the long term (i.e., after taper), patients originally treated with imipramine or placebo did as well at follow-up as patients treated with alprazolam, without the problems of physical dependence and discontinuation that any long-term alprazolam therapy entails”.

Interestingly, Clum et al. (1993) subsequently identified some methodological weaknesses in Clum’s (1989) early analysis. Using more stringent inclusion criteria, the more recent meta-analysis continues to support some of the earlier conclusions. In particular, the antidepressants continued to be identified as a treatment of choice (although dropout rates were high) and psychological interventions were supported once more as a treatment of choice, with exposure or flooding being identified as a successful treatment. However, the support for the high-potency benzodiazepines was much weaker than it had been in the earlier analysis, perhaps because the earlier analysis had included some clinical trials, with no control groups, that included only data from people who completed the trials.

In summary, it appears that the efficacy of the cognitive behavioral therapy therapies is equaling, and sometimes surpassing, that of the pharmacotherapies. Furthermore, given the difficulties associated with medications, such as side-effects and the possibility of dependence, psychological interventions should be the treatment of choice for panic disorder and agoraphobia. Pharmacotherapies may be preferred because of their initial low cost; however, the cost of continuing medication and the hidden cost of the higher rates of relapse have yet to be factored into the equation.

However, with the relatively recent emergence of the selective serotonin re-uptake inhibitors it is premature to draw strong conclusions about these drugs. Nevertheless, the data to date are promising. Finally, although rarely discussed in the literature, just as there are some patients who find the prospect of medication unacceptable, there are some who will not participate in a cognitive behavioral therapy program. Given that the success of a cognitive behavioral therapy program relies upon active participation, for these individuals pharmacotherapies may be preferred.