Saturday, November 15, 2008

Trends in Psychiatry

The medical field is just like any other kind of human endeavor: subject to fads and herd mentality. While we’d all like to think that doctors rely only on science and only care about the best available evidence, doctors are people, too. Like everyone else, doctors are heavily influenced by what other people think, and the opinions of their medical peers are very important in determining practice patterns. In addition, doctors must function in an environment where information is usually insufficient. We don’t know enough about how any part of the body works, yet all these parts can have problems, and doctors are expected to fix them when they do. Filling in these knowledge gaps is more art than science, and in this artistic facet of medicine, most doctors seek the consensus of their peers---medicine is a field for creative renegades only on TV.

So, each medical specialty has its own trends, which vary over time and by geographic region. This is by no means peculiar to psychiatry; all areas of medicine experience this same phenomenon, but here we are concerned with the effect of psychiatric fads on treatment of people with developmental disorders.

Major Tranquilizers: The Original Fad

The field of psychopharmacology didn’t really exist until the first antipsychotic drugs became available in the 1950’s. The first generation of antipsychotics, like Thorazine and Mellaril, revolutionized psychiatry by allowing direct biomedical treatment of psychosis. These “major tranquilizers” were powerful drugs with a wide range of effects (good and bad) which could actually treat schizophrenia and other major thought disorders for the first time. Unfortunately, the enthusiasm for these drugs was a bit overdone, and many people who were never psychotic were prescribed antipsychotics anyway. Why? As an old professor of mine used to say, “When all you have is a hammer, everything starts to look like a nail!” Nowhere did this megatrend of the 50’s cause more problems than in the medical management of developmental disorders. Enormous numbers of people with DD were prescribed major tranquilizers for a wide range of symptoms. In some cases, the drugs had genuine benefits, but in many others, the main effect was non-specific sedation. Decades later, the chickens finally came home to roost, as thousands of people with developmental disorders were diagnosed with irreversible, drug-induced movement disorders.

Nowadays, these older antipsychotics are rarely used, and seldom prescribed to children. However, we may be seeing a similar phenomenon in our time. The newest generation of antipsychotics, usually called “atypical antipsychotics”, are being prescribed in vast quantities to children and adults with developmental disorders. In part, this is because this class of drugs represents a significant advance compared to the older antipsychotics, though some critics argue that the differences in practice are not that great, and the real push is coming from pharmaceutical companies. Indeed, while the new drugs are more easily tolerated by patients, and they appear to be somewhat more effective in their primary indication, the treatment of schizophrenia, they are not the “silver bullet” many had hoped for. Risperdal (risperidone) became the first atypical antipsychotic actually marketed for the treatment of autism after a large and well-done study showed efficacy in treating the irritability and behavior problems associated with autism. The multicenter trial described below led to FDA approval of Risperdal for this indication, the first formal approval of any treatment for autism.

N Engl J Med. 2002 Aug 1;347(5):314-21.

Risperidone in children with autism and serious behavioral problems.

McCracken JT, McGough J, Shah B, Cronin P, Hong D, Aman MG, Arnold LE, Lindsay R, Nash P, Hollway J, McDougle CJ, Posey D, Swiezy N, Kohn A, Scahill L, Martin A, Koenig K, Volkmar F, Carroll D, Lancor A, Tierney E, Ghuman J, Gonzalez NM, Grados M, Vitiello B, Ritz L, Davies M, Robinson J, McMahon D; Research Units on Pediatric Psychopharmacology Autism Network.
University of California, Los Angeles, USA.

BACKGROUND: Atypical antipsychotic agents, which block postsynaptic dopamine and serotonin receptors, have advantages over traditional antipsychotic medications in the treatment of adults with schizophrenia and may be beneficial in children with autistic disorder who have serious behavioral disturbances. However, data on the safety and efficacy of atypical antipsychotic agents in children are limited. METHODS: We conducted a multisite, randomized, double-blind trial of risperidone as compared with placebo for the treatment of autistic disorder accompanied by severe tantrums, aggression, or self-injurious behavior in children 5 to 17 years old. The primary outcome measures were the score on the Irritability subscale of the Aberrant Behavior Checklist and the rating on the Clinical Global Impressions - Improvement (CGI-I) scale at eight weeks. RESULTS: A total of 101 children (82 boys and 19 girls; mean [+/-SD] age, 8.8+/-2.7 years) were randomly assigned to receive risperidone (49 children) or placebo (52). Treatment with risperidone for eight weeks (dose range, 0.5 to 3.5 mg per day) resulted in a 56.9 percent reduction in the Irritability score, as compared with a 14.1 percent decrease in the placebo group (P<0.001). The rate of a positive response, defined as at least a 25 percent decrease in the Irritability score and a rating of much improved or very much improved on the CGI-I scale, was 69 percent in the risperidone group (34 of 49 children had a positive response) and 12 percent in the placebo group (6 of 52, P<0.001). Risperidone therapy was associated with an average weight gain of 2.7+/-2.9 kg, as compared with 0.8+/-2.2 kg with placebo (P<0.001). Increased appetite, fatigue, drowsiness, dizziness, and drooling were more common in the risperidone group than in the placebo group (P<0.05 for each comparison). In two thirds of the children with a positive response to risperidone at eight weeks (23 of 34), the benefit was maintained at six months. CONCLUSIONS: Risperidone was effective and well tolerated for the treatment of tantrums, aggression, or self-injurious behavior in children with autistic disorder. The short period of this trial limits inferences about adverse effects such as tardive dyskinesia.

This would seem to be good news, and in most ways it is. A commonly used treatment for autism spectrum disorders was shown to be efficacious in autistic children; this is good evidence that this drug and other atypical antipsychotics treat some of the most difficult symptoms of developmental disorders. However, all drugs have side effects, and antipsychotics have more than most. Some of these are well known and well described. For example, a number of movement disorders, some irreversible, can occur with these medications. Fortunately, newer drugs are less likely to cause these problems, especially at the lower doses usually prescribed in developmental disorders. However, they seem to have some special problems of their own, like pronounced weight gain in younger patients, and unusual side effects such as this:

J Child Adolesc Psychopharmacol.

Risperidone-induced enuresis in two children with autistic disorder.

Hergüner S, Mukaddes NM.
Department of Child and Adolescent Psychiatry, Istanbul Faculty of Medicine, Istanbul University, Istanbul, Turkey.

INTRODUCTION: Risperidone appears to be effective in treating behavioral problems in children with autistic disorder. Although increased appetite, weight gain, and sedation are among the most common side effects, risperidone-induced enuresis is rarely reported. METHOD: We will present two cases with risperidone-induced enuresis, and discuss our findings in the context of current literature. RESULTS: Two children aged 11 and 10 years, diagnosed with autism and mental retardation, have developed new-onset diurnal and nocturnal enuresis respectively on their first and second weeks of risperidone monotherapy (1.5 and 1 mg/day). They did not experience sedation, and their medical history and workup were unremarkable. As enuresis did not resolve spontaneously, we decided to substitute risperidone with olanzapine. Enuresis ceased rapidly after discontinuation of risperidone with no emergence when patients were treated with olanzapine 5 mg/day for a period of 6 months and 1 year, respectively. DISCUSSION: Although the pathophysiology of antipsychotic-induced enuresis remains unclear, a number of mechanisms including alpha(1)-adrenergic blockade, dopamine blockade, and antimuscarinic effects has been proposed. Olanzapine has lower alpha(1)-adrenergic and dopaminergic blockade properties, thus changing risperidone to olanzapine may be an alternative modality in risperidone-induced enuresis when antipsychotic treatment is crucial. Clinicians should be more vigilant about screening for this side effect, especially in younger population with developmental disabilities.

Urinary incontinence is not usually associated with treatment with older antipsychotics, yet the newer drugs can cause this with surprising frequency in younger patients with DD.
By itself, this isn’t a show-stopper, but this illustrates an important point. When a drug which is useful, but perhaps not the first choice in most cases, becomes the only drug actually officially approved for that indication, it suddenly becomes the first choice of many risk-averse doctors. Thus, Risperdal became the first choice for the treatment of all autism spectrum disorders, in the eyes of many physicians. That could be a big problem in the end, with atypical antipsychotics becoming more popular than their first-generation cousins ever were. While we’d like to think that these are simply better drugs, and their popularity is well-deserved, we may not know the whole story. People with MRDD suffer from a wide range of symptoms, and many are better treated with other classes of medications. Risperdal and other atypical antipsychotics may be the first choice for some of these symptoms, but they’re certainly not the first choice for most.