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Panic Disorder |
Overcoming Anxiety (Home) > Panic Disorder > Selective Serotonin Re-uptake Inhibitors Selective Serotonin Re-uptake Inhibitors (SSRIs)During a recent NIMH Algorithm Development Meeting, the expert panel reached the conclusion that the SSRIs had become the pharmacological treatment of choice for PD. There is now a large body of evidence documenting that SSRIs are effective and probably deserve to be the pharmacological treatment of choice in PD for many patients. SSRIs have been available for a decade, and include fluvoxamine, fluoxetine, paroxetine, sertraline and citalopram. All of them have proved capable of reducing panic attacks and agoraphobia in PD patients. A series of placebo-controlled trials have demonstrated that fluvoxamine is superior to placebo in the treatment of PD.There are several studies comparing the efficacy of fluvoxamine with other agents. In a study comparing fluvoxamine with clomipramine, both drugs were effective, but the positive effects of clomipramine occurred earlier and were somewhat superior to those of fluvoxamine. In a comparison of fluvoxamine with brofaromine (a reversible MAOI), no significant differences were found. Den Boer and Westenberg, comparing fluvoxamine with maprotiline (a specific norepinephrine re-uptake blocker), found that the patients on fluvoxamine experienced a significant decrease in panic attacks and in the other symptoms of PD. Significant improvement, however, was not seen in the maprotiline patients, but when maprotiline patients were switched to fluvoxamine, most of them responded well . According to the authors, this is one of the clearest studies suggesting that serotonin medication is more efficacious than a noradrenergic drug. On the other hand, other studies support the efficacy of noradrenergic drugs, such desipramine and nortriptyline. After eight weeks in an open trial with citalopram, 13 out of 17 patients had responded in terms of an antipanic effect. Sixteen of the patients continued in a 15-month long-term maintenance trial, with 11 of them completing this portion of the study. Initial gains were maintained throughout this longer period, with further improvement in some patients, including two patients who had failed to respond in the initial eight-week trial. There was no tolerance to early positive effects. The mean dose of citalopram fell from 41 mg/day after eight weeks to 38 mg/day at the end of the 15-month trial. Bertani et al. reported a positive response in four of the five patients on 20–40 mg/day. Longer-term follow-up studies of citalopram in PD are underway following the trial described above and preliminary results suggest maintenance of positive acute effects for over a year. Paroxetine was the first SSRI to obtain a licensed indication for PD and has been the most extensively studied SSRI in PD. A large trial , carried out in 39 centres in 13 countries, provided definitive evidence of paroxetine efficacy. This trial involved 367 patients randomised to paroxetine, clomipramine and placebo. Patients from this study could choose at the end of the 12-week trial whether they wanted to enter a long-term extension of the study for nine months or be titrated off over a three-week period. Patients were abruptly discontinued from paroxetine and there was no evidence of withdrawal syndrome. Two large, double-blind, placebo-controlled, flexible-dose trials have been completed with sertraline , and will be discussed as one trial. In total, 342 patients from 20 US and Canadian centres were randomised to either sertraline or placebo. Dosages began at 25 mg/day for one week, and were then increased to between 50 and 200 mg/day based on clinical response and tolerability over the 10-week trial. Panic attack frequency was reduced significantly more in the sertraline group, beginning in the second week and was sustained throughout each week of the trial. Significant differences between sertraline and placebo emerged in the first week on ‘‘Panic Attack Burden’’ (the frequency of attacks multiplied by their severity): the percentage of patients who had no attacks was higher than the percentage on placebo, and the reduction of panic attacks was greater than for placebo as early as weeks two and four. Although controlled trials for fluoxetine in PD are underway, these have not yet been presented or published. Results from open trials indicated efficacy of fluoxetine in PD treatment. Paroxetine is the only SSRI that has a clear target dose (40 mg). For the sertraline, there is some suggestion that 100–150mg might be the recommended dosage range. Fluoxetine in the range between 20 and 80 mg has been associated with response. Fluvoxamine has been demonstrated to be effective at 50–150 mg. The patients should begin treatment with as low a dose of the medication as can be practically arranged. Trials comparing paroxetine with clomipramine found that paroxetine’s action was somewhat more rapid, there was reduction of more of the ancillary symptoms of PD in long-term maintenance on paroxetine, and paroxetine had significantly fewer side-effects. Studies comparing fluvoxamine with clomipramine suggested that the two agents are approximately equal or clomipramine was more effective than fluvoxamine in reducing anxiety and depressive symptoms. In a trial comparing citalopram and clomipramine, both drugs were effective, with little reported differences. In the absence of adequate direct comparison, it would be difficult to compare SSRIs in terms of side-effects. They seem to share a cluster of side-effects (nausea, asthenia, etc.); whether there are lower rates of these various symptoms with one agent or another will have to wait for trials on direct comparisons. In conclusion, there is now a large body of evidence that SSRIs are effective and probably deserve to be the pharmacological treatment of first choice in PD for many patients.
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