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TOPIC A review of major depressive disorder and antidepressant drug treatment in children and adolescents. PURPOSE This paper provides a synthesis of current information regarding diagnosis, psychobiology, psychopharmacology, and practice guidelines for psychiatric nurses involved in the treatment of depression in children and adolescents. SOURCES Recent journal and book publications regarding the psychopharmacological treatment of depression in children and adolescents. CONCLUSION Although there is far less research to guide the psychopharmacological treatment of depression in children and adolescents than there is for adults, these treatments can be safely administered and effective for some individuals in this age group.

This study characterizes the childhood environment of adult women having panic disorder with agoraphobia, with particular emphasis placed on parental rearing practices, family conflict resolution, experiences of sexual mistreatment, problematic childhood indicators, and childhood separation experiences. The retrospective research design included attitudinal and behavioral indicators for 80 female patients diagnosed with panic disorder with agoraphobia, and a control group of 100 female volunteers with no history of psychiatric illness. Study findings did not support evidence of parental overprotection, parental death, devorce, or sexual mistreatment as risk factors. Results did suggest the significance of childhood separation anxiety, a conflicted family environment, lack of parental warmth and support, and the presence of chronic physical illness and substance abuse in the chilhood home of patients, as well as more emotional, family, alcohol, and school problems as children and adolescents.

Diazepam-binding inhibitor (DBI) is a neuropeptide that has been detected in the brain and cerebrospinal fluid (CSF). Previous studies have suggested the possible role of DBI as a potential endogenous anxiogenic ligand modulating GABAergic transmission at the benzodiazepine-GABA receptor complex. The measurement of DBI immunoreactivity (DBI-IR) in CSF of panic-disorder patients and normal controls was undertaken to assess whether there were differences in the CSF concentration of this peptide to assess possible relationships with other monoamines and peptides. Lumbar CSF was obtained from 18 panic patients (4 men, 14 women) and 9 controls (5 men, 4 women). As a group, no significant differences were found between panic patients' CSF concentration of DBI-IR (1.12 +/- 0.27 pmol/mL) and normal volunteers (1.23 +/- 0.27 pmol/mL). No gender differences were demonstrated. However, we did find a positive correlation between CSF levels of DBI and CSF corticotropin releasing hormone (CRH) in our panic patients.

Objective: Preclinical and clinical evidence suggests that central opioid dysfunction may play a role in the pathophysiology of the eating disorders. In particular, endogenous opioids are known to regulate feeding behavior, mood, perception, and neuroendocrine function, all ofwhich are disturbed in patients with eating disorders. Although low concentrations of CSF �3-endorphin have been reported in low-weight patients with anorexia nervosa, central opioid activity in normal-weight patients with bulimia nervosa has not been reported. The authors therefore measured CSF concentrations of �-endorphin and dynorphin in drug-free female patients with DSM-III-R-defined bulimia nervosa and normal comparison subjects. Method: After 4 days ofa low monoamine diet and overnight bed rest, CSF was obtained (12-26 cc) I rom 1 1 women with bulimia and 1 7 normal comparison subjects (eight women and nine men). Results: The women with bulimia had significantly lower CSF concentrations of �3-endorphin than did the female comparison subjects. However, CSF concentrations of dynorphin were not significantly different in patients and female or male comparison subjects. �3-Endorphin concentrations were inversely correlated with Beck Depression Inventory scores and the depression subscale ofthe Eating Disorders Inventory. Conclusions: These data support a role for central opiates in the mediation of the pathophysiology of the signs and symptoms of bulimia nervosa, although it is impossible to rule out the effects of depression on the results. (Am J Psychiatry 1992; 149:1086-1090)

The literature on panic disorder is summarized with regard to epidemiological, environmental, cultural, psychological, family, and genetic factors. Laboratory provocation of anxiety is reviewed with emphasis on the noradrenergic model of panic from a biological perspective. Positron emission tomography results involving brain asymmetries in lactate-sensitive panic patients are discussed, as are the psychopharmacological agents currently effective in the treatment of panic disorder. It is suggested that psychiatric nurses base their clinical practice on a holistic understanding of treatment implications as they relate to an individual's broader functioning. Areas for future nursing research are also identified.

Magnetic resonance imaging (MRI) brain scans were performed on 12 patients with obsessive-compulsive disorder and 12 healthy controls. Measurements of the area of the head of the caudate nucleus, cingulate gyrus thickness, intracaudate/frontal horn ratio, and area of the corpus callosum did not differ between the two groups. These limited data do not support the presence of a consistent gross brain structural abnormality in obsessive-compulsive disorder. Further studies using other anatomic measurements and other brain structural imaging techniques are warranted.

Nurses working with adolescents need an understanding of the clinical syndrome of bulimia in order to identify individuals at risk for this disorder and implement preventive and therapeutic interventions. The epidemiology, early precipitants, physiology, and biochemistry of bulimia nervosa are reviewed. From this integrated framework, implications for treatment are explored with an emphasis on holistic nursing care including health education.

This study characterizes the early family experiences of 30 women with bulimia nervosa and 15 women with major depression, and compares them with 100 women controls, with particular emphasis placed on parental rearing practices, family conflict resolution, sexual mistreatment, problematic childhood indicators, and childhood separation experiences. There is little research on these patient populations in relation to their childhood experiences, and thus, it is difficult to identify markers for women at risk for these disorders. The findings show that there are significant differences between the experiences these women had growing up and those of the control group, and a profile of children at risk based upon the study indicators is presented.

Normal-weight bulimic patients have disturbed appetite, mood, and neuroendocrine function and often respond to antidepressants. Since these findings suggest abnormalities in brain monoaminergic pathways, the authors measured CSF monoamine concentrations in 27 normal-weight bulimic patients and 14 volunteers. Bulimic patients had a significantly lower mean CSF norepinephrine concentration. Levels of CSF 5-HIAA, the major serotonin metabolite, and CSF HVA, the major dopamine metabolite, were normal, although more frequent binge-eating in bulimic subjects was associated with a significantly lower CSF HVA level. Whether trait- or state-related, monoaminergic disturbances are part of this disorder's neurobiological syndrome. The lower CSF norepinephrine concentration suggests bulimia is not simply a variant of affective disorders.

Cholecystokinin concentrations in the CSF of 25 patients with panic disorder and 16 normal comparison subjects were ascertained by radioimmunoassay. The patients with panic disorder had significantly lower CSF concentrations of cholecystokinin, which may reflect increased CNS cholecystokinin receptor sensitivity, reduced numbers of receptors, or a compensatory reduction in cholecystokinin octapeptide secondary to theoretically increased central cholecystokinin tetrapeptide activity.

Investigation of the potential role for endogenous opiates as a modulator of anxiety states has yielded variable results. Increased plasma [3-endorphin has been reported accompanying surgical stress (Pickar et al 1982) and with high anxiety ratings in women during menstruation (Veith et al 1984). Can" et al (1986) found no significant change in plasma [3-endorphin during lactate infusion before and after treatment with alprazolam in panic disorder patients or controls but did note a slight decrease in 13-endorphin over time secondary to acclimatiza~'ion. Dager et al (1989) found higher 13-endorphin levels in panic disorder than in depressed patients and a slight decrease in plasma [3-endorphin during lactate infusion in panic disorder patients, depressed patients, and controls. George et al (1989) found significantly higher

Cerebrospinal fluid (CSF) concentrations of corticotropin-releasing factor (CRF) were measured in a group of patients with anxiety disorders and normal comparison subjects (NC) to explore the hypothesis that abnormalities in CRF neuronal regulation occur in patients with anxiety disorders. Analysis of variance (ANOVA) revealed no differences in CSF CRF concentrations between the four diagnostic categories: panic disorder (PD), generalized anxiety disorder (GAD), obsessive-compulsive disorder (OCD), and NCs. Male OCD patients had higher CSF CRF concentrations than men with PD and GAD and male NCs. CSF CRF concentration was positively correlated with age in women but not in men. These findings suggest that central neuronal CRF regulation may be affected by both age and gender.

Objective The authors' goal was to assess dexamethasone for the treatment of depression. Method Thirty-seven outpatients (11 men and 26 women) meeting DSM-III-R criteria for major depressive disorder were randomly assigned to receive either placebo or 4 mg/day of oral dexamethasone for 4 days. Baseline Hamilton depression scale scores were compared with scores obtained 14 days after the first dose of study medication. Data were analyzed by using two-sample t tests, chi-square methods, and Fisher's exact test. Results Seven (37%) of the 19 patients given dexamethasone but only one (6%) of the 18 patients given placebo responded positively. No adverse events or side effects were reported, and all patients who entered the study completed it. Conclusions A brief course of oral dexamethasone (4 days) was significantly more effective than placebo within 14 days for the treatment of depression in a randomized, double-blind study of depressed outpatients.

Cholecystokinin octapeptide (CCK-8) appears to modulate appetitive behavior, and in rodents, anxiety-related behavior. The authors studied CCK-8 in patients with bulimia nervosa. CSF concentrations of CCK-8 were measured in 11 drug-free female patients with DSM-III-R-defined bulimia nervosa and in 16 normal subjects. The bulimic patients had significantly lower levels of CCK-8 than the comparison subjects. CCK-8 concentrations were inversely correlated with scores on the anger-hostility, anxiety, and interpersonal sensitivity subscales of the SCL-90-R. They were not significantly correlated with age, percentage of standardized average body weight, or mean weekly frequency of binge eating or vomiting. The results indicate that central CCK-8 abnormalities may play a role in the pathophysiology of bulimia nervosa.

In a study of 45 patients with anxiety disorders and 11 control subjects, mean cerebrospinal fluid (CSF) concentrations of thyrotropin-releasing hormone (TRH) were not significantly different between nonpsychiatric control subjects and those with panic disorder, generalized anxiety disorder, or obsessive-compulsive disorder. Male subjects, regardless of diagnosis, had significantly higher mean CSF concentrations of TRH than females.

While many data suggest that Obsessive-Compulsive Disorder (OCD) is an illness accompanied by dysregulation of the serotonergic system, interesting clinical evidence and animal studies also suggest possible dysregulation of the dopaminergic (DA) system. In order to determine whether clomipramine (CMI), an antiobsessional agent, is capable of altering DA function, we performed a neuroleptic radioreceptor assay (NRRA) on plasma samples from OCD patients before and after treatment in a double-blind, placebo controlled trial of CMI. CMI produced mild but significant DA D-2 receptor binding activity in an in vitro assay. The degree of dopamine binding activity did not correlate with clinical response to clomipramine. Because it has been suggested that another drug with antiobsessional efficacy, fluoxetine, may also have dopamine blocking properties, it may be speculated that antidopaminergic activity in combination with serotonergic effects is involved in antiobsessional activity of effective agents for some patients.

Psychiatric nurses in inpatient settings play a critical role in the management of potentially violent patients. One of their primary objectives is to ensure the safety of patients and staff 24 hours a day. This requires skillful observation of patients' motor behavior, verbal clues, and change in mental status, which may indicate an increase in agitation or possible aggressive behavior. It requires experience in prevention strategies and skill in acute crisis intervention techniques. To effectively intervene with potentially violent patients, psychiatric nurses must be able to work well under stress and be able to organize and execute a plan of immediate action. After the acute stage of the patient's illness, nurses should focus their work on assisting patients to manage their own behavior and supporting their newly acquired skills.

A recently reported multinational, 8-week double-blind, placebo-controlled study assessing the efficacy of alprazolam versus placebo in the treatment of panic disorder indicated significant differences favoring alprazolam. We now report the results of a three-site, 6-week, double-blind, fixed-dose study comparing alprazolam 2 mg, alprazolam 6 mg, and placebo in 94 patients with panic disorder with or without agoraphobia. Both alprazolam treatment groups (6 mg and 2 mg) improved significantly more than did the placebo treatment group on most outcome measures. Only a few statistically significant differences between the 6 mg and 2 mg alprazolam groups were discerned, although the pattern of treatment response across measures suggested a dose effect. Dropouts in the placebo group were primarily due to lack of efficacy and in the alprazolam 6 mg group were due to side effects, which may have contributed to the limited differences between groups at study end. The findings suggest that many patients may require less than 6 mg of alprazolam per day for effective treatment of panic disorder.

Prostaglandins are thought to act as neuromodulators of both central catecholamine and endocrine systems. Abnormalities of these systems have been described in affective disorders, in general, and in agoraphobia with panic attacks, in particular. This study measured basal prostaglandin-E (PGE) cerebrospinal fluid (CSF) levels in 20 patients with agoraphobia with panic attacks and 10 nonpsychiatric controls. In a subgroup of patients and controls, CSF levels of adrenocorticotrophic hormone (ACTH) and corticotropin-releasing factor (CRF) were also measured. There was no significant difference in CSF PGE levels between patients and controls. However, patients with higher depression scores had lower CSF PGE levels. CSF PGE levels tended to correlate with CSF ACTH, but not CSF CRF in the patient group, in general, and in the female patients, in particular. These findings do not support an abnormality in basal CNS PGE production in agoraphobia with panic attacks, but suggest further study of the PGE modulatory effect on the hypothalamic-pituitary-adrenal axis in this disorder.

Sleep electroencephalograms (EEGs) of subjects with primary panic disorder were compared to those of normal controls matched for age and sex. Significant differences were found between patients and controls in sleep latency, sleep efficiency, and stage 2 sleep duration. No differences were found between the two groups in REM latency. Because depressed patients are known to have reduced latency to REM sleep, these data add support to the hypothesis that panic disorder and depression are distinct disorders.

Patients diagnosed as having agoraphobia with panic attacks by DSM-III criteria were evaluated with the dexamethasone suppression test (DST). Depressive symptoms were assessed using the Beck Depression Inventory, the Depression Scale of the Minnesota Multiphasic Personality Inventory, and the Hamilton Rating Scale for Depression. Of 97 patients tested, 12.4% had a positive DST. These findings are consistent with earlier reports that found an incidence of abnormal DSTs between 11% and 15% in agoraphobic patients. Abnormal DSTs did not correlate with levels of depression on any of the depression measures.

The authors relate their clinical experience with 46 panic disorder patients who were receiving 3-10 mg/day of alprazolam. Fifteen (33%) developed symptoms consistent with DSM-III criteria for major depression despite remission of their panic symptoms. Clinicians should be alert to this potentially reversible complication.

Earlier reports indicated that phenelzine treatment may result in clinically significant reductions of vitamin B6 in some individuals. Sixteen subjects, ages 21-59 years (seven men, nine women) with panic disorder with or without agoraphobia were treated with an average of phenelzine 53.5 mg/day for an average of 10 weeks in an open treatment study. No significant effects on plasma levels of pyridoxal phosphate, the active form of vitamin B6, were discernible in this group, nor was there any clear relationship between pyridoxal phosphate levels and symptoms in the subgroup of five patients who did develop deficiency-type symptoms. Pyridoxine replacement had unclear effects in symptomatic patients.