ABSTRACT
OBJECTIVE: To examine the impact of age on the effects of desipramine (DMI) on autonomic input to the heart. METHOD: Twenty-four-hour electrocardiograms were obtained from 42 subjects, aged 7 to 66 years, while off and on DMI. To obtain measures of autonomic input to the heart, heart rate variability was assessed via spectral analysis of RR interval variability. RESULTS: DMI treatment was associated with a significant increase in 24-hour mean heart rate and significant decreases in RR interval variability in all spectral bands, including in the high-frequency band, which provides a measure of parasympathetic input to the heart. RR interval variability was greater in younger individuals both off and on DMI. CONCLUSIONS: DMI treatment was associated with a marked decline in RR interval variability, indicating that DMI affects autonomic input to the heart. Specifically, DMI reduced parasympathetic input, which, in theory, may increase vulnerability to arrhythmias. However, the magnitude of DMI's impact on RR interval variability did not vary with age.
Subject(s)
Antidepressive Agents, Tricyclic/pharmacology , Desipramine/pharmacology , Heart Rate/drug effects , Adolescent , Adult , Age Factors , Aged , Arrhythmias, Cardiac/chemically induced , Arrhythmias, Cardiac/physiopathology , Child , Female , Heart/innervation , Humans , Male , Middle Aged , Parasympathetic Nervous System/drug effects , Parasympathetic Nervous System/physiologyABSTRACT
OBJECTIVE: In light of recent reports of sudden death in children being treated with desipramine (DMI), 3 of which were associated with physical exercise, the authors examined the effects of DMI on exercise in children and adults before and during DMI treatment. METHOD: Before treatment, 22 subjects (9 children, 13 adults) participated in a graded treadmill exercise test. Outcome measures included exercise tolerance, cardiovascular, and electrocardiographic parameters at progressive intensity levels and serum norepinephrine (NE) levels before and after exercise testing. Subjects were then treated with DMI, titrated to an average DMI dosage of 3 mg/kg, and underwent repeated exercise testing. RESULTS: DMI treatment was associated with a significant elevation of circulating NE levels in the pre-exercise assessment. Exercise tolerance was not affected by DMI, and blood pressure and heart rate effects were modest. The cardiovascular impact of DMI treatment was similar in children and adults. One 31-year-old subject exhibited a brief episode of ventricular tachycardia associated with exercise during DMI treatment. CONCLUSIONS: DMI has only minor effects on the cardiovascular response to exercise, and these effects do not appear age-related. However, DMI may increase the risk of exercise-associated arrhythmias in rare individuals.
Subject(s)
Antidepressive Agents, Tricyclic/pharmacology , Cardiovascular System/drug effects , Depression/prevention & control , Desipramine/pharmacology , Exercise Test/drug effects , Adolescent , Adult , Age Factors , Antidepressive Agents, Tricyclic/adverse effects , Arrhythmias, Cardiac/etiology , Blood Pressure/drug effects , Child , Desipramine/adverse effects , Exercise , Exercise Tolerance/drug effects , Female , Heart Rate/drug effects , Humans , Male , Norepinephrine/bloodABSTRACT
BACKGROUND: Chronic depressions commonly present in youth and cause significant morbidity. No treatment studies in this age group are currently available. METHODS: 19 pediatric subjects with dysthymic disorder or 'double depression' were recruited. After four weeks of psychosocial treatment, subjects failing to improve began open treatment with fluoxetine (20 mg) for eight weeks. Subjects were then reassessed for treatment response. RESULTS: Fifteen subjects entered the medication phase, and eleven (73%) no longer met criteria for dysthymic disorder or Major Depression at final assessment. CONCLUSIONS: Fluoxetine shows promise as a safe and effective treatment for youth with chronic depressions. Controlled trials are indicated. LIMITATIONS: Open label design, no comparison treatment condition. CLINICAL RELEVANCE: As in adults, treatment with antidepressants may prove to be a useful intervention with children and adolescents with chronic forms of depression.
Subject(s)
Antidepressive Agents, Second-Generation/therapeutic use , Dysthymic Disorder/drug therapy , Fluoxetine/therapeutic use , Adolescent , Antidepressive Agents, Second-Generation/pharmacology , Child , Dysthymic Disorder/psychology , Female , Fluoxetine/pharmacology , Humans , Male , Treatment OutcomeABSTRACT
In a randomized double-blind crossover study of children with attention deficit hyperactivity disorder (ADHD), the time course effects of four doses of Adderall (5, 10, 15, and 20 mg) and an inactive (placebo) control, and an active (Ritalin) control were evaluated. A laboratory classroom setting was established in which subjective (teacher ratings of deportment and attention) and objective (scores on math tests) measurements were taken every 1.5 hours across the day. In addition to significant time and dose effects of Adderall, significant time-of-day effects were documented in the placebo condition for the subjective measure of deportment and objective measures of performance. Regression analyses were used to estimate the magnitude of these baseline effects. Correlations across time were used to evaluate the test-retest reliability of each measure in the face of these time-dependent placebo effects. After placebo/time adjustments, within-subject correlations between pairs of measures were used to evaluate the validity of the math test as a measure of response to stimulant medication.
Subject(s)
Amphetamines/therapeutic use , Attention Deficit Disorder with Hyperactivity/drug therapy , Attention Deficit Disorder with Hyperactivity/psychology , Central Nervous System Stimulants/therapeutic use , Adolescent , Child , Double-Blind Method , Female , Humans , Male , Methylphenidate/therapeutic useABSTRACT
Multiple dependent variables were graphed for 29 subjects who participated in a double-blind evaluation of 4 doses of Adderall, plus positive (methylphenidate) and placebo control conditions. Five judges ranked the conditions for each subject, and analyses of individual subjects indicated that these rankings were concordant (reliable) across judges. Consensus rankings were assigned to each subject, and an analysis of these ranks showed that the conditions differed significantly. The choice of best conditions were judged to be across 3 doses of Adderall (10, 15, and 20 mg). This confirms the clinical impression of individual differences in optimal dose of stimulant medication. The methodological, graphical, and statistical methods presented in this article provide a systematic, reliable procedure for evaluating relative response of individuals to different doses of stimulant medication.
Subject(s)
Amphetamine/therapeutic use , Attention Deficit Disorder with Hyperactivity/drug therapy , Central Nervous System Stimulants/therapeutic use , Amphetamine/adverse effects , Attention Deficit Disorder with Hyperactivity/psychology , Central Nervous System Stimulants/adverse effects , Child , Cross-Over Studies , Data Display , Double-Blind Method , Humans , Observer Variation , Research DesignABSTRACT
Many therapeutic approaches to managing suicidal behavior among youth have been used, including in-school education programs, screening programs, telephone hotlines, cognitive behavioral therapies, medication management, and inpatient milieux treatment programs. These interventions have been applied based on educational and therapeutic principles drawn from prior work with adolescents in varied scholastic and psychiatric settings. This article reviews: the assessment of risk factors among suicide attempters, emotional states, family, social isolation, interpersonal loss, substance and alcohol abuse, and treatment strategies.
