Brian J. McConville

Nicotine for the treatment of Tourette's syndrome.

Recent evidence has demonstrated that nicotine may obtund the symptoms of Tourettes syndrome (TS). TS is a neuropsychiatric disorder characterized by motor and vocal tics, obsessions and compulsions, and frequently with impulsivity, distractibility, and visual-motor deficits. While neuroleptics, such as haloperidol, are most effective for treatment of the motor and vocal tics of TS, these medications have many side effects. In this article, we review the evidence, consistent with findings in animals, that administration of nicotine (either 2 mg nicotine gum or 7 mg transdermal nicotine patch) potentiates the therapeutic properties of neuroleptics in treating TS patients and that a single patch may be effective for a variable number of days. These findings suggest that transdermal nicotine could serve as an effective adjunct to neuroleptic therapy for TS.

Nicotine potentiates the effects of haloperidol in animals and in patients with Tourette syndrome

Nicotine was found to markedly potentiate haloperidol-induced hypokinesia in rats. Nicotine alone was without effect. Subsequently, concurrent administration of 2 mg nicotine gum to 10 Tourette syndrome patients being treated with haloperidol produced a substantial decrease in tics and improvement of concentration and attention span. Nicotine gum alone was without effect. While 80% of children showed improvement with nicotine gum, 70% completely discontinued the gum because of side-effects, primarily involving nausea and bitter taste. Nicotine may prove useful for treating other neuroleptic responsive disorders, such as schizophrenia and Huntingtons disease.

Long-Term Safety, Tolerability, and Clinical Efficacy of Quetiapine in Adolescents: An Open-Label Extension Trial

Quetiapine is a novel, atypical antipsychotic agent that has been shown to provide long-term efficacy without serious adverse effects in adults. This is the first study of the extended use of quetiapine in adolescents. Five boys and 5 girls, ages 12.3 to 15.9 years, with diagnoses of schizoaffective disorder (n = 7) or bipolar disorder with psychotic features (n = 3) were eligible for entry into this single-site, 88-week, open-label trial. Subjects had completed a pharmacokinetic study over 23 days, during which the dosage of quetiapine was increased sequentially from 25 mg bid to a maximum of 400 mg bid (800 mg/day) (McConville et al. 2000). In the open-label extension of this trial, which followed directly after this trial, a physicians choice design allowed for flexible dose titration of quetiapine by the study physician to an optimal dose for each patient, with ending doses ranging from 300 mg/day to 800 mg/day. Concomitant medications, especially for anxiety and/or manic symptoms, were allowed as deemed necessary. Tolerability and safety were assessed using clinical laboratory tests, physical examinations, measurements of vital signs, interviews for selective symptomatology, and electrocardiograms. Psychiatric measurements included the 18-item Brief Psychiatric Rating Scale (BPRS), the Clinical Global Impression (CGI) scale, and the modified Scale for the Assessment of Negative Symptoms (SANS). Neurologic symptom ratings included the Simpson-Angus Scale and the Abnormal Involuntary Movement Scale. Mean BPRS, CGI, and SANS scores improved significantly during the trial (p < 0.05). No extrapyramidal symptoms or evidence of tardive dyskinesia was seen. Clinically, there was a nonsignificant increase in mean weight and body mass index at week 64. This long-term study suggests that quetiapine is a well-tolerated antipsychotic agent that is efficacious for the treatment of symptoms of selected psychotic disorders in adolescents.

The psychiatric diagnoses of twenty-two adolescents who have sexually molested other children

The purpose of this study was to assess the prevalence of specific psychiatric disorders in adolescents who have sexually molested other children. Twenty-two adolescent males (aged 13 to 17 years) who sexually molested a child at least once were evaluated with structured clinical interviews for DSM-III-R axis I disorders. All subjects met lifetime DSM-III-R criteria for pedophilia (with the exception of the age requirement), 21 (95%) for two or more paraphilias, 18 (82%) for a mood disorder (12 [55%] for a bipolar disorder), 12 (55%) for an anxiety disorder, 11 (50%) for a substance use disorder, and 12 (55%) for an impulse-control disorder. Also, 12 (71%) of 17 subjects were diagnosed with attention-deficit/hyperactivity disorder, and 16 (94%) with conduct disorder. We conclude that some adolescent child molesters may have pedophilia or other paraphilias. Other axis I disorders with impulsive features, especially conduct, attention-deficit/hyperactivity, bipolar, and substance use disorders, may also be found in these adolescents.

Nicotine potentiates haloperidol-induced catalepsy and locomotor hypoactivity

Nicotine was found to potentiate the catalepsy and reduced locomotion following the administration of haloperidol. The ability of various doses of nicotine (0.1, 0.2, or 0.3 mg/kg) to potentiate the catalepsy produced by haloperidol (0.1, 0.2 or 0.4 mg/kg) was investigated. Nicotine potentiated the cataleptic effects of both the 0.2 and 0.4 mg/kg doses of haloperidol, but had no effect following the lowest (0.1 mg/kg) dose of haloperidol. The nicotine potentiation of catalepsy produced by the highest dose of haloperidol was independent of the dose of nicotine used. Nicotine alone did not produce catalepsy. A second experiment evaluated the ability of nicotine to potentiate the decreases in spontaneous locomotor activity produced by haloperidol. Animals received nicotine (0.1 mg/kg) alone or in conjunction with haloperidol (0.1 or 0.4 mg/kg) and were tested in Digiscan Animal Monitors. Haloperidol produced a dose-related decrease in locomotion. Nicotine significantly potentiated the hypoactivity produced by both doses of haloperidol. These results indicated that: 1) nicotine produces a significant potentiation of both the catalepsy and locomotor decreases following haloperidol and 2) the Digiscam Animal Activity Monitors may provide a more sensitive assessment of the interaction between nicotine and haloperidol than the catalepsy bat test. These data suggest that adjunct treatment with nicotine may prove useful for treating neuroleptic responsive disorders such as Tourette Syndrome, schizophrenia and Huntingtons disease.

Transdermal nicotine for Tourette's syndrome

The present review evaulates the therapeutic response to the transdermal nicotine patch (TNP) in Tourettes syndrome (TS) patients. Twenty TS patients (17 children and adolescents, 3 adults), in 18 of whom tic symptoms were not controlled with neuroleptics and 2 of whom were free of medication, were followed for various lenghts of time following the application of two TPs (each 7mg/24 hours). While there was a broad range in individual response, it was determined that each application of a single TNP produced a significant reduction in Yale Global Tic Severity Scale mean scores for an average duration of approximately 1 to 2 weeks post‐application. Individual case reports are discusssed as well as the possible therapeutic mechanisms of transdermal nicotine in reducing the symptoms of TS. Although our data should be viewed as preliminary until controlled studies are completed, the present open‐trial findings suggest that transdermal nicotine is an effective adjunct to neuroleptic theraphy of TS. Drug Dev. Res. 38:290–298.

Pediatric bone marrow transplants: psychological aspects.

On a pediatric bone marrow transplant unit, hematologistoncologists, nurses, social workers, psychiatrists, psychologists, and others on the team deal with children and adolescents whose cancers are either treatable by marrow transplantation or are ultimately fatal. Contrary to original assumptions, many children and families cope well, especially in relatively uncomplicated cases with good outcome. Treatment may include direct psychotherapeutic intervention with the child and family, as well as use of psychopharmacologic agents such as antidepressants or anxiolytics for frank psychiatric disorders. Psychotherapists often have to function adjunctively with other staff members in their interactions with the patient and the family. A stress disorder model appears to best explain child, parent and family reactions to bone marrow transplantation. Given the medical severity and complexity of the conditions treated, and the approximately equal rates of overall success and failure, a supportive consultative approach is usually most helpful for child patients, parents and staff throughout the procedure. A retrospective study of the children treated over seven years in a tertiary pediatric hospital bone marrow transplant unit is presented. The level of child, parent, and family psychopathology was usually mild to moderate, but there were clear differences between patients. Mothers were more supportive than fathers under this extreme type of stress. Prospective longitudinal studies of children and families are needed to establish causal chains and optimal therapeutic interventions.

Personality disorders in first- and multiple-episode mania

We compared rates of DSM-III-R personality disorders in 33 first-episode and 26 multiple-episode bipolar patients. Patients were evaluated with the patient and personality disorders versions of the Structured Clinical Interview for DSM-III-R. Significantly more multiple-episode patients (65%) met DSM-III-R criteria for a personality disorder than did first-episode patients (33%). Race was also associated with a diagnosis of a personality disorder. Personality disorders may be associated with multiple affective episodes in bipolar patients.

NEWER ANTIDEPRESSANTS: Beyond Selective Serotonin Reuptake Inhibitor Antidepressants

This article outlines the use of alternative agents to TCAs and SSRIs. Features of the more commonly used alternative antidepressant agents are outlined. In addition, antidepressant agents that are currently either under development or used in other countries are indicated for completeness because it seems likely that many of these will be introduced in the United States within the next few years. Many of these agents will be used by pediatricians and child psychiatrists for treatment of depression in children, and although much further research is needed, the future for alternative antidepressants and augmenting strategies is extremely promising.

Lower dosages of phentermine-fenfluramine given in the afternoon: five cases with significant weight loss.

Phentermine and fenfluramine are widely used in the treatment of obesity. Despite the fact that primary pulmonary hypertension and mitral valve insufficiency have been associated with fenfluramine use, many of these patients need medication to achieve weight loss. Small degrees of weight loss have been shown to significantly improve obesity-related medical conditions such as hypertension, hypercholesterolemia, and noninsulin-dependent diabetes mellitus. Current practice is to give phentermine and fenfluramine in the morning and afternoon. Doses for phentermine have ranged from 15 to 37.5 mg and for fenfluramine from 20 to 120 mg per day. We report five cases of severely obese women with medical complications who were treated with phentermine 8 mg twice per day (at 1:00 p.m. and 4:00 p.m.) and fenfluramine 20 mg per day (at 4:00 p.m.). Because many obese patients skip breakfast and eat more in the afternoon and evening, medication was dosed in order to cover these high-risk eating periods. Overall, these patients lost a mean of 22.4% of their initial weight (range 18.6% to 32.8%) over an average of 8.4 months (range 3.5 to 16 months). These cases suggest that short-term weight loss can be achieved with a low dose of fenfluramine when both medications are given in the afternoon to better target the eating patterns of obese subjects.