Children depression

In 2004 the FDA urged drug companies to adopt a Don t ask don t tell policy with respect to their clinical-trial data showing that antidepressants are not better than placebos for depressed children. If the data were made public, they cautioned, it might lead doctors to not prescribe antidepressants. The FDA believed that... 

BEHAVIOURAL MODIFICATION IN DEPRESSED CHILDREN HEAD AND TRUNK MOVEMENTS BEFORE AND AFTER TREATMENT DURING CLINICAL INTERVIEWS... 

Depression. Depressed children and adolescents are often irritable and argumentative. They may also be inattentive and easily distracted. A depressed child therefore potentially looks and behaves much like a child with ADHD. In such cases, one should not immediately make both diagnoses. First, treat the child for depression. If the symptoms of ADHD remain after the depression has resolved, then and only then does it make sense to diagnose and treat ADHD as well. 

Preskorn, S.H., Weller, E., Hughes, C., and Weller, R. (1986) Plasma monitoring of tricyclic antidepressants defining the therapeutic range for imipramine in depressed children. Clin Neuropharma-col 9 265-267. 

Indicative of serotonergic dysfunction, abused children with depression were shown to exhibit increased prolactin, but normal cortisol responses to the injection of E-5-hydroxytryptophan, a precursor of 5-HT, as compared to nonabused depressed children and controls (Kaufman et ah, 1998). Likewise, increased prolactin responses to fenfluramine were observed in boys with adverse rearing environment (Pine et ah, 1997). Since prolactin, but not cortisol release, is mediated via 5-HTia receptors, these findings suggest sensitization of these receptors due to early-life stress. Another study recently reported that children with traumatic brain injury (TBl) who had experienced abuse have dramatic increases in CSE concentrations of glutamate, compared to nonabused TBI children (Ruppel et ah, 2001). 

Geller, B., Cooper, T.B., Zimerman, B., Frazier, J., Williams, M., Heath, J., and Warner, K. (1998) Lithium for prepubertal depressed children with family history predictors of future bipolarity a double-blind, placebo-controlled study. / Affect Disord, 51 165-175. 

REM sleep (Rush et ah, 1998). In one of the few sleep studies of children and adolescents treated with fluoxetine, similar findings were noted, with increased light stage 1 sleep, increased number of arousals and REM density, and a largely unaffected REM latency (Armi-tage et ah, 1997). One must keep in mind that studies of depressed children and adolescents suggest that subjects may have sleep polysomnographic abnormalities associated with depression itself (Emslie et ah, 2001). 

Paroxetine pharmacokinetics in 30 depressed children and adolescents of ages 6 to 17 demonstrated substantial interindividual variability and more rapid clearance in youths than in adults (Findling et ah, 1999). Nevertheless, paroxetine may be given once daily in the pediatric population. 

Geller, B., Cooper, T.B., and Chestnut, E.C. (1985a) Serial monitoring and achievement of steady state nortriptyline plasma levels in depressed children and adolescents preliminary data. / Clin Psychopharmacol 5 213—216. 

The safety and efficacy of combined SSRI and stimulant pharmacotherapy have been addressed in two open studies. Gammon and Brown (1993) reported on the successful addition of fluoxetine to stimulants in the treatment of 32 patients with ADHD with comorbid depressive and anxiety disorders (Gammon and Brown 1993). These children with comorbid conditions had failed to respond to methylphenidate alone. Another report detailed the addition of methylphenidate to SSRI treatment (Findling, 1996). Depressed children and adults with comorbid ADHD were treated with either fluoxetine or sertraline. While depressive symptoms remitted, ADHD symptoms persisted. Methylphenidate was added and successfully treated the ADHD symptoms. In both investigations, the combined treatment was well tolerated. 

Factors associated with increased risk for recurrence in naturalistic studies of depressed children and adolescents may serve as guidance to the clinician to decide who needs maintenance treatment. These factors include history of prior depressive episodes, female sex, late onset, suicidality, double depression, subsyndromal symptoms, poor functioning, personality disorders, exposure to negative events (e.g., abuse, conflicts), and family history of recurrent MDD (<2 episodes) (Birmaher et ah, 1996 a,b Goodyer et ah, 1998 Fewin-sohn et ah, 1999 Rao et ah, 1999 Rueter et al., 1999 Weissman et ah, 1999a, b Klein et ah, 2001). 

Emslie, G., Rush, A.J., Weinberg, A.W, Kowatch, R.A., Hughes, C.W, Carmody, T., and Rintelmann J. (1997b) A doubleblind, randomized placebo-controlled trial of fluoxetine in depressed children and adolescents. Arch Gen Psychiatry 54 1031-1037. 

Findling, R.L., Reed, M.D., Myers, C., Riordan, M.A., Fiala, S., Branicky, L., Waldorf, B., and Blumer, J.L. (1999) Paroxetine pharmacokinetics in depressed children and adolescents. / Am Acad Child Adolesc Psychiatry 38 952-959. 

Geller, B., Fox, L.W., and Clark, K.A. (1994) Rate and predictors of prepubertal bipolarity during follow-up of 6- to 12 year-old depressed children. / Am Acad Child Adolesc Psychiatry 33 461-468. 

Kovacs, M. and Goldston, D. (1991) Cognitive and social cognitive development of depressed children and adolescents. / Am Acad Child Adolesc Psychiatry 30 388-392. 

Stein, D., Williamson, D.E., Birmaher, B., Brent, D.A., Kaufman, J., Dahl, R.E., and Ryan, N.D. (2000) Parent-child bonding and family functioning in depressed children and children at high-risk and low risk for future depression. / Am Acad Child Adolesc... 

Sovner et al. (1998) have done an excellent job summarizing the data on antidepressants in patients with developmental disabilities. There have been nine reports of antidepressant use in adults with depression and MR and three reports of antidepressant use in children and adolescents. Eight of nine reports in adults were positive. The drugs studied included nialimide (n = 27), fluoxetine (9), imipramine (6), amoxapine (2), and nortriptyline (1) (total n = 45). In addition, Sovner et al. identified four reports of antidepressant use in children. One involved successful treatment with fluoxetine in an adolescent, another indicated efficacy with imipramine and amitriptyline in 9 of 12 children (Do-sen, 1982), and a third showed successful management in 3 of 4 children treated with imipramine or tryptophan plus nicotinamide (Dosen, 1990). One study of fluoxetine in depressed children with autism and MR witnessed improvement in depression but not in compulsive symptoms (Ghaziuddin and Tsai, 1991). 

Magnus RD, Findling R, Preskorn SH, et al. An open-label pharmacokinetic trial of nefazodone in depressed children and adolescents [Abstract], Psychopharmacol Bull 1997 33 550. 

Olfson, M., Marcus, S. C., Shaffer, D. 2006, Antidepressant dmg therapy and suicide in severely depressed children and adults a case-control study, Arch.Gen.Psychiatry, vol. 63, no. 8, pp. 865-872. 

Newman (2004) also made the point that the FDA found that only 3 of the 15 available controlled clinical trials showed efficacy for antidepressants in treating depressed children. He said that several FDA committee members spoke in favor of the antidepressants, citing either their own experience or the TADS conducted by NIMH however, others and I found the evidence of efficacy much less convincing than the evidence of harm. According to Newman,... 

The FDA report also mentioned that no completed suicides were recorded among all the trial subjects. The agency failed to emphasize that the no suicides occurred on placebo either. Leaving depressed children drug-free did not produce a single suicide. This wholly contradicts the tendency to give drugs to prevent suicides. 

I have observed for more than a decade (Breggin, 1991c, 1997a) that there is no scientific evidence that antidepressants are helpful for depressed children. But as a headline in Clinical Psychiatry News indicated a dozen years ago, Though Data Lacking, Antidepressants Used Widely in Children (Baker, 1995). 

A controlled clinical trial found that fluoxetine caused a 6% rate of mania in depressed children and youngsters age 7-17 (Emslie et al., 1997). The reactions were severe enough to cause the children to be dropped out of the trials. By contrast, none of the depressed youngsters... 

Subsequently, the UK Committee on Safety of Medicines issued guidance for practitioners, indicating that with the exception of fluoxetine, the benefit-harm balance of SSRIs and venlafaxine in depressed children and adolescents was unfavorable (27). A similar conclusion was drawn concerning mirtazapine. It is, however, puzzling that the therapeutic effects of fluoxetine should be quite so different from compounds that are similar pharmacologically. One important issue might be the relevance of regulatory trials of antidepressants to real-world treatment. Placebo-controlled trials in depression... 

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