Psychopharmacology UpdateAG Awad, MD, FRCPC, Professor of Psychiatry, University of Toronto; Director, Psychopharmacology Program, The Clarke Institute of Psychiatry division of the Addiction and Mental Health Corporation; Past-President, Canadian College of Neuropsychopharmacology, Toronto, Ontario.
Haloperidol Plasma Levels and Dose Optimization
Coryell W, Miller D, Perry PJ. Am J Psychiatry 1998;155:48–53.
This study was designed to test the utility of haloperidol plasma level determinations in the management of patients with schizophrenia who show an initially poor response to haloperidol. Patients with the established diagnosis of schizophrenia who were in an acute relapse were randomly assigned to receive fixed haloperidol doses intended to achieve plasma levels of 8 to 18 ng/ml or levels of 25 to 35 ng/ml. Patients who failed to improve on the Brief Prescribing Rating Scale by at least 30% were then subject to a dose reassignment. The results indicated that patients who had haloperidol plasma levels below 18 ng/ml experienced more improvement than those with higher haloperidol plasma levels.
Over the past 10 years, a noticeable change has taken place in the neuroleptic dosages that are used in the treatment of schizophrenia. Currently in North America it is more common for neuroleptics to be prescribed in relatively lower dosages than they once were.
The few studies that contributed to this change have done so by pointing to the superior efficacy of lower doses and the improved therapeutic index—a result of fewer side effects. In this context, this well-designed, well-executed study adds further support to the superiority of using lower doses of haloperidol, which is in line with more emerging literature. It is clear from this and other studies that the patients who fail to respond to low dosages are also unlikely to benefit from much higher dosages. With the recent introduction of several new neuroleptics, the clinician obviously has more therapeutic options, although certainly at a higher acquisition cost.
This study also demonstrates the utility of neuroleptic blood level measurements in optimizing clinical management. Haloperidol is ideal in terms of having very few metabolites, and its levels can be measured in commercial laboratories. I do not believe that haloperidol levels need to be measured routinely in clinical practice because this adds some additional cost to the provision of care at a time when we must be concerned about containing health costs. There is no reason to order blood levels for a patient who seems to be responding adequately and experiencing minimal side effects. On the other hand, this approach can be useful for patients who fail to respond or are experiencing several side effects in the face of what is considered a low dosage.
Mood Stabilizer Combinations: A Review of Safety and Efficacy
Freeman MP, Stoll AL. Am J Psychiatry 1998;155:12–21.
Through a manual and computer (MEDLINE) search, the authors review safety and efficacy data on the more frequently used combinations of mood-stabilizing agents. The authors conclude that there have been only a few controlled studies on the use of combinations of mood stabilizers in the treatment of refractory bipolar disorder. While the interactions of such combinations are often useful, sometimes they are complex and dangerous. The authors conclude that following one general rule, adding medications to the patient’s current regimen in modest doses and allowing for slow dose increases, may reduce the risks of serious drug interactions. From the review, the safest and most efficacious mood stabilizer combinations appear to be the mixtures of anticonvulsants and lithium, in particular valproic acid plus lithium.
The introduction of the tricyclic antidepressants and lithium in the 1950s ushered in an era of optimism that changed the management of mood disorders. In recent years, newer classes of more selective and safer antidepressants were introduced as were the roles of several anticonvulsant medications, such as carbamazepine and valproic acid, which have become well-established mood stabilizers. Despite these major advances and the availability of more pharmacological options, however, fewer patients with bipolar disorder benefit from monotherapeutic approaches. Particular subtypes, such as those patients with mixed episodes or rapid cycling, can be refractory to lithium treatment as a mood stabilizer. In the face of these challenging clinical situations, concomitant use of more than one mood stabilizer has often been used in the treatment of such refractory patients. Therefore, the importance of this paper is that it attempts to put some order into the literature regarding the value or lack of value of mood stabilizing combinations and their safety. The results clearly indicate that the addition of valproate to lithium is considered the first line of treatment for manic states that are refractory to lithium monotherapy. Conversely, the treatment of choice for acute mania with partial but inadequate response to valproate is to add lithium. The data presented suggest that, generally, the addition of valproate is most effective for patients with rapid cycling or mixed episodes, because patients receiving the combination were less likely to suffer a relapse than were patients receiving lithium and placebo. A reassuring feature of the combination is that lithium’s pharmacokinetics were found to be unchanged by valproate. In addition, in one study it was reported that there was no significant difference in adverse events reported by the group of patients who received valproate and lithium compared with the group that received added placebo and lithium. Potential side effects of the valproate–lithium combination include possible additive adverse reactions such as sedation, gastrointestinal problems, tremor, and weight gain. Overall, the combination of lithium and valproate appears to be well tolerated and effective in treating refractory bipolar illness based on the available data.
On the other hand, the use of a carbamazepine–lithium combination may pose potential problems related to the complex carbamazepine pharmacokinetics and the possibility of drug interactions. Most reports, however, suggest that the safety of the lithium–carbamazepine combinations is considered to be adequate, although the available data do indicate that the lithium–valproate combination is less problematic.
In clinical practice, monotherapy is clearly more preferable than polypharmacy; however, in certain situations one must consider a combination of medications of the same class. I believe that polypharmacy is neither good nor bad, but should only be called upon in situations where the patient has failed to respond adequately to monotherapeutic approaches. Good clinical practice dictates that if such an approach is used the clinician has to be clear about the objectives of such combinations. The clinician must closely monitor any emergent adverse events and must also establish a time framework to avoid exposing the patient to the potential high risk of toxic or adverse events without accomplishing any further clinical improvement. In essence, the clinician has to establish the risk and benefits of such combinations on a regular basis.
Donald Wasylenki, MD, FRCPC, Professor of Psychiatry and Health Administration,
Faculty of Medicine, University of Toronto, Toronto, Ontario.
Self-Help and Consumer Initiatives
One of the most important and dramatic changes as regards the planning and operation of mental health services has been the emergence of consumer participation. Indeed, until recently it has been said that the mental health system worked on the premise that the customer is always wrong!
With an increased understanding of processes of rehabilitation and recovery, most mental health professionals and the agencies responsible for the reform of mental health systems have come to understand the importance of empowerment and self-sufficiency in overcoming disability and have recognized the tremendous fund of information that service users hold. With the increase in consumer participation, a greater emphasis has been placed on traditional self-help approaches and on newer consumer initiatives.
Traditional self-help programs are based upon the principle that people who share a common experience are able to help one another in ways that cannot be offered by professionals. The number of self-help groups in the mental health field has grown substantially during the past 2 decades, partially aided by support from public funds and private foundations. Such groups tend to provide both emotional support and task-oriented assistance to members who sometimes refer to themselves as consumers or survivors. According to Chamberlin, self-help groups may be categorized as follows: groups whose members promote the illness model (The Depression and Manic Depression Association of Canada, Schizophrenia Society of Canada), groups that provide self-help in conjunction with treatment for illnesses (Recovery Inc), groups whose members see themselves as consumers (National Mental Health Consumers Association), and groups who see themselves as liberationists (National Association of Psychiatric Survivors) (1). Rootes and Aanes list 7 criteria that define self-help groups and which distinguish them from other types of organizations, such as advocacy groups (2). These criteria include supportive and educational aims; focus on a single life-disrupting event; support for personal change; anonymous and confidential membership; voluntary membership; member leadership; and absence of a profit orientation. The key features appear to be a commitment to personal empowerment and interpersonal support.
Beyond the traditional self-help model, programs have been established that promote the role of disabled individuals as active consumers of mental health services. This is an expanded notion of self-help and implies the taking of direct action by consumers. Organizations that developed to achieve this objective have been described as consumer initiatives, which distinguishes them from the more individually focused self-help model. Increasingly, these organizations are supported by public funds and may include activities such as advocating, participating in the planning and delivery of services, operating drop-in centres, educating the public and professionals, and establishing and operating consumer-run businesses (economic development activities). In Ontario, 36 Consumer/Survivor Development Initiative (CSDI) projects, funded by the Ontario Ministry of Health, are in operation. Twenty-eight of these are organizations that develop activities and initiatives which reflect consumer interests; 6 are cooperative businesses; one is a provincial business council; and one is diagnostically focused, involving both consumers and family members. All are democratically operated, independent, and consumer/survivor-controlled. In a survey of all 36 organizations, 7 areas of activity were identified: 1) mutual support; 2) advocacy; 3) cultural activities; 4) knowledge development and skills training; 5) public education; 6) educating professions; and 7) economic development.
Recently, research on self-help and consumer initiatives has been reviewed (3). Although these approaches do not lend themselves to the conduct of rigorous studies, there is empirical support for the establishment of self-help and consumer initiatives for users of mental health services. A study of Recovery Inc. showed that participants reported decreases in nervousness, tension, and depression after joining groups, and long-term group members reported a diminished need for psychotherapy and medication and increased feelings of general well-being (4). Members of another self-help group, Grow International, were hospitalized for fewer days over a 32-month period than matched controls. Subjects in both groups had histories of chronic and severe psychiatric illness (5). Chamberlin and others surveyed members of 6 self-help programs in various parts of the United States and found that respondents reported positive or highly positive effects of self-help when rating their general satisfaction with life (78.4%) and when rating how successful their life had been (72.1%). Other reported benefits were increased positive feelings and help fulfilling life goals (6). With regard to consumer initiatives, Trainor and colleagues carried out a multi-dimensional study of the Ontario CSDI projects (unpublished observations). A sample of 194 consumer members of CSDI organizations listed their use of formal mental health services for equivalent periods before and after becoming members. Results demonstrated that service use in all categories declined substantially. The most significant declines were in the use of inpatient and crisis services. Admissions to hospitals, outpatient visits, and private physician visits were significant as well.
It is generally acknowledged that support for self-help and consumer initiatives should be part of any modern mental health reform strategy. Evidence of effectiveness exists, particularly with regard to reducing reliance on formal mental health services and thus, presumably, increasing feelings of autonomy and self-sufficiency, but it requires more rigorous demonstration. The evolution of more sophisticated qualitative and participative research methodologies has the potential to enrich our understanding of these important approaches.
1. Chamberlin J. The ex-patients’ movement: where we’ve been and where we’re going. The Journal of Mind and Behaviour 1990;11(3):323–36.
2. Rootes LE, Aanes DL. A conceptual framework for understanding self-help groups. Hospital and Community Psychiatry 1992;43(4):379–81.
3. Health Canada. Review of best practices in mental health service delivery. Forthcoming.
4. Galanter M. Zealous self-help groups as adjuncts to psychiatric treatment: a study of Recovery Inc. Am J Psychiatry 1988;145(10):1248–3.
5. Kennedy M. Psychiatric hospitalization of GROWERS. Paper presented at the Biennial Conference on Community Research and Action. East Lansing (Michigan); 1989.
6. Chamberlin J, Rogers S, Ellison ML. Self-help programs: a description of their characteristics and their members. Psychiatric Rehabilitation Journal 1996;19(3):33–42.