National Association for Rights Protection and Advocacy

Recent developments in psychopharmacology

Peter Stastny, M.D.
Associate Professor of Psychiatry
Albert Einstein College of Medicine
September 2003

Newly emergent side-effect profiles of "atypical" and older antipsychotics:

The addition of several new "atypical" antipsychotics in the last few years (Geodon = ziprasidone; Seroquel = quetiapine; Abilify = aripiprazole) with each being touted as an improvement over their predecessors, has been accompanied by the emergence of serious, at times life-threatening side-effects. Diabetes mellitus has been the most consistently mentioned problem, which has recently prompted the FDA to issue a labeling request for a warning pertaining to this risk for all six atypical antipsychotics (Zyprexa = olanzapine, Risperdal = risperidone, Geodon = ziprasodone, Clozaril = clozapine, Seroquel = quetiapine, and Abilify = aripiprazole). Cardiac conditions including potentially fatal arrhythmias, obesity, hyperlipidemia, and atherosclerosis, have also been noted with alarming frequency. In addition to earlier data that have indicated a shorter life-expectancy for persons receiving long-term neuroleptic treatment, these problems may further increase the chances of premature death and serious medical complications. There are a host of other disturbing side-effects such as irreversible tardive dyskinesia, Parkinsonism, sexual and menstrual dysfunctions, gastro-intestinal symptoms, cognitive problems, etc., associated with these drugs that have been marketed as being largely free of precisely those kind of problems.

Increasing use of anti-epileptic medications for various indications:

For many years, anti-convulsants such as carbamazepine (Tegretol), valproic acid (Depakote) and clonazepam (Klonopin) have been used in the treatment of mood disorders, particularly those with manic episodes. More recently, these and several other newer anti-convulsants (gabapentin = Neurontin; topiramate = Topamax; lamotrigine = Lomictal) have been used for additional, often unclear purposes. Augmentation of antipsychotic effects; mood stabilization; curtailment of violent outbursts; anti-depressant effects; personality disorders (i.e., borderline personality), have all been mentioned to justify their addition to other psychotropic medicines. They are rarely, if ever, used as a sole agent for psychiatric conditions. Such uses are not approved by the FDA, and are therefore not listed as indications in the Physicians’ Desk Reference.

Massive increase in psychopharmacological treatments for children and adolescents:

Most medications used for adults have been increasingly used for children, at times including those of pre-school age. ADD/ADHD is the most frequent indication, but depression, mood-disorder and psychosis are also increasing. Behavioral problems traditionally not subject to pharmacological treatments are increasingly seen as appropriate target symptoms. Similarly to adults, many medications are combined, for example stimulants, antidepressants (TCI1 & SSRI), mood stabilizers and antipsychotics. This is a development that exceeds the scope of my presentation.

New FDA-approved indications for SSRIs:

In the last decade SSRIs,2 which have originally been marketed primarily as anti-depressants have been used for a great variety of diagnoses, such as most anxiety disorders (generalized anxiety, phobia, panic, post-traumatic stress [PTSD], obsessive-compulsive disorder [OCD]; eating disorders; and ADD/ADHD3. Only recently, a small number of these indications have been approved by the FDA, specifically Zoloft (sertraline) and Paxil (paroxetine) for PTSD, Paxil for social phobia, and Proxac (fluoxetine) and Luvox (fluvoxamine) for OCD. While some of these developments may be beneficial for certain individuals suffering from intractable conditions, especially OCD and PTSD, they have been accompanied by aggressive, consumer-directed advertising campaigns, that have led to considerable overuse.

Polypharmacy - concomitant use of multiple agents:

In a challenge to evidence-based treatments and state coffers, ever increasing numbers of psychotropic agents are being prescribed in combination, with the result that recently discharged individuals arrive at the doorsteps of outpatient departments carrying large plastic bags with scores of medicine bottles. It is not unheard of for three anti-psychotic medications to be combined, in addition to mood stabilizers (mostly anti-convulsants), antidepressants, sedatives, and anti-cholinergics (for side-effect management), leaving some individuals with as many as eight or nine different drugs to contend with. This is apart from any additional medications needed to treat their medical conditions. Aside from the burden and the risk placed on the individual patient, this has become a challenge to public health departments nationwide who are facing exploding costs for these drugs (in excess of $ 1000 per month for some patients) prompting some states (including Connecticut) to look at ways to curtail these expenses, much to the chagrin of doctors and drug manufacturers. As of this time, there are very few, if any, peer-reviewed studies demonstrating that such practices are safe or effective.

Increased use of benzodiazepines in emergency situations:

The one piece of good news that has developed during the last decade is the increasing use of benzodiazepines in emergency situations, often replacing high-potency injectable neuroleptics. Most people brought to psychiatric emergency rooms in a state of agitation would generally be given an injection of haloperidol, resulting in very frequent acute muscular reactions (dystonia) with less than desired effects. It appears that many psychiatrists are now more inclined to use intramuscular lorazepam (Ativan) or diazepam (Valium) with much better results and fewer side-effects.

1  TCI = tricyclic antidepressants

2  SSRI = Selective serotonin reuptake inhibitor

3  ADD = Attention Deficit Disorder; ADHD = Attention Deficit Hyperactivity Disorder

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