It is self-evident that any new psychotropic drug is likely to be expensive. This situation also applied to the drugs used to treat other chronic illnesses such as cardiovascular disease, rheumatoid arthritis and diabetes. However, the cost of treatment implies more than the price of the drug. As most psychiatric disorders are chronic, costs must take into account the acute, maintenance and prophylactic phases of treatment. Thus in assessing the true cost, it is necessary to consider the ancillary procedures needed to monitor the patients' response to treatment (laboratory tests, etc.), managing any adverse effects of the medication, the relative costs of inpatient versus out-patient treatment, costs saved to the social and health services as a result of improved compliance and better response to treatment and the comparative costs of alternative treatments. It has been estimated that the cost of a new psychotropic drug for the treatment of depression, bipolar disorder or schizophrenia is approximately 10-15% of the total cost of treatment. It is also necessary to take into account the costs of not providing adequate treatment. These factors include the risks of premature death, and the increased morbidity, including the loss of productivity and the adverse effect of the illness on the social life of the patient.
Thus despite the much higher cost of a new psychotropic drug, Quality of Life assessments, which take into account the true cost of treatment, consistently show that new antidepressants and antipsychotics are superior to the older, and cheaper, medications. Most importantly, when optimal total care is provided for the patient, the quality of life is substantially improved which surely must be the aim of clinical psychopharmacology.
The limitation of pre-clinical studies on the development of novel psychotropic drugs
Serendipity has played a major role in the discovery of most classes of psychotropic drugs. For example, the observation that the first anti-depressants, the tricyclic antidepressants and the monoamine oxidase inhibitors, impeded the reuptake of biogenic amines into brain slices, or inhibited their metabolism, following their acute administration to rats, provided the experimenter with a mechanism that could be easily investigated in vitro. Such methods led to the development of numerous antidepressants that differed in their potency, and to some extent in their side effects (for example, the selective serotonin reuptake inhibitors) but did little to further the development of novel antidepressants showing greater therapeutic efficacy. The accidental discovery of atypical antidepressants such as mianserin led to the broadening of the basis of the animal models used to detect potential antidepressants with greater emphasis being placed on the chronic effects of the drugs in vivo. However, with few exceptions, all the in vitro and in vivo models in current use are based on the acute effects of novel compounds. Recently, with the impact of high-throughput screening methods based on the activity of compounds on multiple neurotransmitter receptors in vitro, even acute in vivo methods have been reduced in an attempt to decrease the time taken to proceed to the initial clinical assessment. Only time will tell whether the extensive use of genomics, microarray screens and receptor profiles of novel compounds will lead to genuinely novel psychotropic drugs. So far, there appears to be little advance in the therapeutic potential of the psychotropic drugs in development.
A comment on the limitation of clinical trials of new psychotropic drugs
A typical placebo controlled trial consists of 50-60 patients including a reference drug. Trials of new psychotropic drugs usually last for 6-8 weeks; the recommended duration of treatment in clinical practice is usually about 6 months. Most clinical protocols do not provide justification for the sample size used, or even specify the statistical power of the data obtained. As the proportion of non-responders for many psychotropic drugs may range from 20-30%, it can be argued that such limited trials (with a statistical power that is too low to show differences between treatments, conducted over too short a period in comparison with clinical practice and often excluding non-compliant patients from the final analysis) are unlikely to show any difference between a new and standard drug. This means that few studies are able to demonstrate an improved efficacy of a new drug over a standard drug. It has been calculated that the sample size that would be required to show a difference of 5% between two psychotropic drugs, assuming that approximately 20% will be non-responders or partial responders, would be between 1250 and 2380 patients per arm of the trial. The expense of such trials would, of course, be prohibitive! This does show that the apparent limited efficacy of most classes of psychotropic drugs is a reflection of the limitation of the clinical trial rather than their real potential differences, which could only be determined by using much larger numbers of patients in trials that last for several months.
Decision-making in the choice of a psychotropic drug
Despite the considerable advances that have been made in psycho-pharmacological research, there are many areas in which objective decisions based on scientific evidence with regard to the choice of the appropriate drug are sparse. In an attempt to overcome this problem, several authors have recently produced prescribing guidelines based on the evidence of the most appropriate drug to use. Such evidence extends from studies that are supported by randomized control trials (highest category), those which are supported by limited controlled trials (alternative category if drugs of the first category are ineffective) to those based on uncontrolled or anecdotal evidence (lowest category, unproven usefulness). A summary of the treatment options for the major psychiatric disorders and for Alzheimer's disease is found at the end of the appropriate chapter.
General principles of prescribing psychotropic drugs
The decision to use a psychotropic drug must take into account the potential risks and benefits. This should be discussed with the patient and/ or carer. Before prescribing, a full evaluation of the symptoms should be made and the diagnosis confirmed. Polypharmacy should be avoided. If a drug combination is necessary, the pharmacodynamic and pharmacokinetic interactions should be considered.
In general, the lowest effective dose of the drug should be used, particularly in elderly patients. Dose titration should be undertaken slowly. Similarly, on discontinuation of a drug, the dose should be reduced slowly, the rate of decrease being decided by the elimination half-life of the drug. Some psychotropic drugs produce a discontinuation syndrome that can usually be avoided by slow withdrawal. In particular, sedatives, anxiolytics and antidepressants can cause withdrawal effects.
In switching drugs, the half-life of elimination that is being stopped should be considered if drug interactions are to be avoided. The time taken for the withdrawal of a drug depends on the duration of treatment; sedatives, antiepileptics and anxiolytics may take several weeks to withdraw.
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