Abstract
Many of us working in psychiatry recognize the limitations of currently available psychotropic drugs and look forward to, if not long for, the introduction of more effective and better tolerated agents. Sadly, the number of introductions of new chemical entities has reduced substantially since the bumper decade of the 1990s and there seem to be very few drugs in development that promise a real advance in treatment. So, we will have to make do with what we have already.
In fact, we can do more than make do: we can do better with the drugs we now have. This is exemplified by Nicola Savill’s study of a manufacturer-sponsored programme to support carers of children prescribed atomoxetine. This is a drug which is effective but with which adverse effects appear some time before any therapeutic benefit is apparent. The support programme assessed in the paper is one in which specialist nurses maintain telephone and text contact with carers of children on atomoxetine during the crucial first 12 weeks of treatment. In total, 346 children were initiated on atomoxetine and 90.5% of these continued with the drug at 12 weeks. This compares very favourably with historical data suggesting a continuation rate of only 61% in patients not registered with a support programme.
Another drug with which we could probably do better is ethyl-eicosapentaenoic acid (EPA), not least because it has such a wide range of therapeutic benefit in both physical and mental health. Nadir Cheema and colleagues have already demonstrated that EPA is an effective and safe treatment for mild to moderate bipolar depression. In this issue, they investigate the cost-effectiveness of this approach, essentially setting the benefits of the treatment (improvement in symptoms; reduced time in hospital) against the costs. The Markov model used suggested significant reduction in overall costs of nearly £3000 in the first year and this alongside clear clinical benefits. In psychiatry, EPA is mainly used in schizophrenia and rarely in bipolar depression. More extensive use in the area would clearly be beneficial.
It might also be argued that depot antipsychotics are underused: they unequivocally reduce rates of relapse and while not assuring compliance, their use does allow accurate assessment of compliance (those noncompliant simply do not turn up for depot appointments). Despite these obvious advantages, there is a reluctance to use depots perhaps because the use of older typical depots was frequently seen as a punitive measure reserved only for miscreant patients. An added irony was that possibly the most toxic form of the drug was given to reluctant compliers. The availability in the last 10 years of depot forms of newer antipsychotics has changed attitudes somewhat. These formulations are probably less likely to cause acute and chronic movement disorders. Matthias Kirschner and coworkers in Switzerland examine the literature relating to attitudes to depot treatment in first-episode psychosis: an area where depots are rarely used. They found broadly negative attitudes of clinicians towards the use of depots in first-episode patients. In one study, around two-thirds of prescribers thought that first-generation depots were inappropriate for use in first-episode psychosis. Actual usage in first-episode patients was even less frequent than these figures suggest. It seems prescribers are hesitant to prescribe a drug which assures compliance without first assessing the patient’s willingness to comply. The argument against this is that the use of second-generation depots in first-episode patients might well be well-tolerated and more convenient and would very probably reduce the risk of relapse. It would be interesting to see how attitudes change as newer formulations become better embedded in practice.
Another widely underused drug is clozapine. Almost all of the literature pertaining to this drug relates to its use in the Western world. This despite the fact that clozapine has been widely used in China, Africa and South America for many years. Owing to this we know little about the use of clozapine in areas affected by what might be called tropical diseases. Emerson Arcoverde Nunes and colleagues report on three cases of the use of clozapine in patients with dengue fever. This is a viral disease spread by daytime-biting mosquitoes which is characterized by amongst other things leucopenia and thrombocytopenia. Clearly leucopenia is problematic in people taking clozapine because of the drug’s association with fatal agranulocytosis. To complicate matters further, the cessation of clozapine almost always results in precipitous psychiatric deterioration. The authors conclude that careful consideration should be given to the continuation of clozapine during a bout of dengue fever, and if stopped, it might well be safely reinstated after the acute illness has abated.
Dopamine-enhancing drugs are the mainstay of treatment for Parkinson’s disease but their use is sometimes withheld for a variety of reasons. While much is known about their effects on psychomotor performance, knowledge of their acute and chronic effects on cognitive function is very limited. A better understanding of their effects in this respect would be beneficial, especially as mild cognitive impairment is common in Parkinson’s. Poletti and Bonuccelli have completed perhaps the most comprehensive review of research examining the cognitive effects of levodopa and dopamine agonists. Their complex observations defy brief summary, but their conclusions demonstrate the vital importance of considering nonpsychomotor effects of dopaminergic agents.
All of the articles in this issue point the way towards better and more effective use of available agents. A subject we will no doubt return to should we come to see the expected fallow period of drug development in psychiatry.