David Behar

Is a familial definition of depression both feasible and valid

On the basis of familial constellations it is possible to separate out most of the unipolar depressive patients that are seen in the hospital. The groups may be called depression spectrum disease, pure depressive disease, and sporadic depressive disease. The sporadic depressive disease group is older at onset and older at index of admission than the other two groups. The depression spectrum disease and pure depressive disease groups are separated by virtue of the fact that there are more episodes of illness in the latter.

Reduction of (3H)-imipramine binding sites on platelets of conduct-disordered children.

Binding characteristics of tritiated imipramine on blood platelets were determined in daytime hospitalized prepubertal children who had mixed diagnoses of conduct disorder (CD) plus attention deficit disorder hyperactivity (ADDH) and in inpatient adolescents who had a history of aggressive behavior. The number of (3H)-imipramine maximal binding sites (Bmax) was significantly lower in the prepubertal patient group of CD plus ADDH; the dissociation constant (Kd) was not significantly different. There were significant negative correlations between Bmax and the Externalizing or Aggressive factors of the Child Behavior Checklist when the CD plus ADDH prepubertal patients were combined with their matched controls and within the adolescent inpatient group. We propose that a decreased platelet imipramine binding Bmax value, as an index of disturbed presynaptic serotonergic activity, is not specific to depression and may be used as a biologic marker for the lack of behavioral constraint in heterogeneous. populations of psychiatric patients.

Obsessive-compulsive disorder in mentally retarded patients

Of 283 mildly to profoundly retarded patients, 10 (3.5%) presented with compulsive behavior that significantly interfered with their daily functioning. Compulsions occurred in the context of obvious cerebral dysfunction and in the absence of anxiety or “ego-dystonic” qualities. The interrater reliability of the differential diagnosis between compulsions, stereotypies, and other repetitive behaviors was good (kappa=.82). A severity rating scale for the compulsive behavior yielded total scores with good interrater reliability (intraclass correlation coefficient=.82). Single items that described observable behaviors had good reliability, while inner resistance and subjective distress were not reliably assessed and contributed little to the total score. The authors suggest that the DSM-III-R diagnosis of obsessive-compulsive disorder be considered in mentally retarded patients, despite the absence of recognizable ego dystonic characteristics. Emphasis should be on the behavioral, externally observable components of the disorder, rather than on inner conflicts and anxiety. Such a diagnostic approach may also benefit nonretarded compulsive patients.

Pharmacokinetics of lithium carbonate in children

The pharmacokinetics in both serum and saliva of a single oral dose of lithium carbonate 300 mg was investigated in nine children aged 9 to 12 years. The serum and saliva concentration-time curves were parallel and biexponential, with a fast distribution phase after the peak at the second hour and a slow elimination phase starting from the 12th hour. The fast phase half-life was 6.0 +/- 1.8 hour in the serum, and 5.8 +/- 1.9 hour in the saliva. The slow phase half-life was 17.9 +/- 7.4 hour in the serum and 15.6 +/- 8.2 hour in the saliva. Lithium was 2.84 +/- 0.86 times higher in the saliva than in the serum, with a saliva/serum r coefficient of correlation of 0.93. A relatively large error was found in predicting serum levels from saliva. There were significant intersubject differences in the saliva/serum ratio, which point to the need for individual ratios in clinical use. On the whole, the pharmacokinetics of lithium in children had the same features as in adults, with a trend toward a shorter elimination half-life and higher total clearance.

Platelet imipramine binding and serotonin uptake in obsessive-compulsive patients.

Platelet imipramine binding was measured in 16 drug‐free nondepressed patients (aged 20‐61 years, mean ± SD 35 ± 8) suffering from obsessive‐compulsive disorder (OCD) and in 16 sex‐, race‐ and age‐matched healthy controls. Imipramine binding capacity and affinity were not different in the 2 groups. Platelet serotonin (5‐HT) uptake capacity, Vmax, was also measured in 15 of these patients and their matched controls. Vmax was significantly higher in the patients (309 ± 149 pmol/109 cells/min) than in the controls (181 ± 110). An increase in platelet 5‐HT uptake supports the involvement of 5‐HT in OCD and may suggest that a hyperactive serotonergic system is present in this disorder.

Flashbacks and posttraumatic stress symptoms in combat veterans.

Of veterans (N = 37) referred to an outpatient clinic for delayed or chronic posttraumatic stress disorder (PTSD), 95.4% had one or more other, psychiatric disorders (mean ± SD = 2.7 ± 1.9): Cannabis abuse (54%), alcohol abuse (49%), dysthymic disorder (49%), opiate abuse (35%), and less frequent disorders including caffeinism (16%). “Flashbacks with disorientation,” a strong memory associated with a feeling of being in or behaving as if in combat, occurred in 72% of alcoholics and 16% of nonalcoholics (P < .02). These three nonalcoholics abused other substances. This and other studies imply the need to develop criteria for chronic PTSD resulting in less overlap with other diagnoses.

Depression occurring in chronically anxious persons

Abstract Chronic lifelong nervousness preceding the onset of depression was reported in 62 of 288 women hospitalized for depression. The depressive syndrome of these patients was characterized by increased incidences of panic attacks, projecting blame, hypochondriasis, fearfulness, and insomnia and by a decreased incidence of psychomotor retardation. The previous personalities of these patients were more likely to be described as worrisome, phobic, demanding, excessively ill, shy, requiring constant reassurance, irritable, complaining, sensitive, and rigid. They were less likely to be described as sociable. They were more likely to have a family history of alcoholism. Their constellation of symptoms closely resembled that of hostile depression.

Quetiapine treatment of adolescent and child tic disorders

Quetiapine reduced major tic disorders in one adolescent and in one child who both had attention-deficit/hyperactivity disorder (ADHD) and tics (a common combination). Diagnoses were based on patients meeting full DSM-IV criteria for both disorders from separate clinical interviews with a parent and the patient. In these cases,amphetamines had improved the quality of their lives and school functioning, but markedly worsened their tics. Quetiapine permitted them to stay on their stimulant. One advantage of quetiapine when compared to other atypical antipsychotics is its minimal hyperprolactinemia [1, 2]. Hyperprolactinemia may contribute to insulin resistance and bone demineralization [3, 4], especially when used with chronic disorders like ADHD. Case 1: A fifteen-year-old male had been diagnosed with severe, disruptive ADHD. Methylphenidate and dextroamphetamine caused marked aggravation of his motor and vocal tics. He had refused all further stimulant trials because of being teased. Yet he had moved from a “D” average to a “B” average on dextroamphetamine. Clonidine (0.1 mg every 8 hours) and guanfacine (1 mg every 8 hours) while on dextroamphetamine reduced tics by 50 %, but this was still unacceptable to the patient. His parents would not consent to further increases of these two alpha2 agonists since he felt sedated and his blood pressure was only 90/65.Nor did they want to use traditional dopamine antagonists fearing tardive dyskinesia, dystonia and cardiac side effects. Tricyclic antidepressants were also rejected. The patient remained on dextroamphetamine. The treatment dose was based on clinical response and not weight. He was initiated on 2.5 mg every five hours, progressively increased by 2.5 mg until weekly school evaluations showed his ADHD was largely controlled and weekly grades were improving. His final effective dose was 10 mg every five hours. However, the patient, his parents and the physician agreed his tics had increased. Tic frequency went from one every 15 minutes to one every 20 seconds and were approximately 300 % more intense. His tics were initially treated with quetiapine (12.5 mg) with one dose in the morning and one in the evening. He experienced only transient fatigue. In a month, he was stabilized at 25 mg each morning and evening. Importantly, the youth became less ambivalent regarding medication. His ADHD remains effectively treated and his tics have been suppressed for a year. Case 2: A nine-year-old boy with Tourette’s disorder and ADHD had been diagnosed by two child psychiatrists from interviews with a parent, the patient and extensive school observation forms. His baseline vocal and motor tics included abdominal jerks, shoulder shrugs, loud throat clearing and constant sniffing noted throughout all interviews. His ADHD had previously failed to respond to methylphenidate (regular and osmotic slow release forms). He was successfully treated with a mixed stimulant of dextroamphetamine and amphetamine (AdderallR). His dose was initiated at 2.5 mg each morning before school and eventually increased by 2.5 mg progressively to 15 mg morning and afternoon. Doses of 12.5 mg produced sub-optimal focus and attention according to both teacher classroom evaluations and homework ratings done by a parent, while 17.5 mg doses increased irritability and tics with no additional ADHD improvement. After a few weeks on 15 mg doses, the patient was started on quetiapine due to increased frequency over his baseline tic frequency. Parent and physician noted J. L. Schaller, M. D. ( ) Chester County Research Center Chester Springs, PA, USA E-Mail: jlschaller@aol.com

Topiramate leukopenia on clozapine

with clozapine 550 mg a day, along with lithium at therapeutic levels, in a residential facility. He met DSM-IV criteria for Bipolar I, Manic Disorder. The latter had been chronic and severe. Starting at age 16, he was sleepless. He had rapid pressured speech that became hard to follow after 2 minutes due to his flight of ideas. He was expelled from three expensive private schools in Europe. While more stable on clozapine, he still designed, made, and exhibited jewelry, composed and recorded songs, wrote a book on psychiatry, took a course in photography, and painted, all simultaneously. He had not used marijuana for 5 years. The mania was unremitting for 7 years.He had been hospitalized a dozen times,and failed to respond to multiple antipsychotics and mood stabilizers. He assaulted staff and family many times. He never committed profit-making crimes. On clozapine, he became quieter, only hypomanic, but no longer dangerous to self or others. However, his mother objected to his 25 kg weight gain.Because he had been so treatment-resistant prior to the use of clozapine, tapering the drug was unwise. Topiramate, as a mood stabilizer, and as an increasingly used weight suppressor,was proposed.His white blood cell count (WBC) had ranged from 9000/μL to 10,000/μL for 2 years on clozapine. Topiramate was added, 25 mg BID for 1 week, 50 mg BID for 1 week, then 100 mg BID for 1 week, and finally, 200 mg BID. Complete blood counts continued every 2 weeks, per the standard clozapine protocol. They were normal for 4 weeks. After 1 week of topiramate 200 mg BID, his WBC was European Child & Adolescent Psychiatry (2004) 13:51–52 DOI 10.1007/s00787-004-0323-0 LETTER TO THE EDITORS

Trends in the Residential (Inpatient) Treatment of Individuals with a Dual Diagnosis.

Clinical trends are discussed with respect to the inpatient treatment of individuals with dual diagnosis. Identified operant trends include the increased attention on functionally derived treatments and treatments designed for infrequent behaviors.