Depressive disorders in children

In this chapter we review extant data on the neurobiology of unipolar and bipolar depressive disorders in children and adolescents. A complement to two recent reviews (Kaufman and Ryan, 1999 Kaufman et ah, 2001), this chapter places primary emphasis on those studies in which neuroimaging techniques have been used. Unfortunately, such studies are few and far between. Preclinical models that have guided research on the neurobiology of affective disorders in adults are discussed, and, given the limits in the application of these models to juvenile samples, especially in the case of unipolar disorder, the need for more developmentally focused preclinical work is emphasized. 

Limitations in the Application of Preclinical Models of Effects of Stress in Organizing Neurobiological Correlates of Major Depressive Disorder in Children and Adolescents... 

Unipolar and bipolar depressive disorders in children and adolescents are serious conditions. The pathophysiology of these disorders is poorly understood. The new tools available through neuroimaging techniques will help to unravel the neuroanatomical systems involved in the onset and recurrence of these disorders. There is a need for more developmentally informed predinical research and more studies of the normal development of the neural systems implicated in emotional regulation. 

Treatment of Major Depressive Disorder in Children and Adolescents... 

An urgent meeting of the Group was convened on 4 June 2003 to consider clinical trial data which had just been received by the MHRA on the safety of paroxetine in the treatment of major depressive disorder in children and adolescents. Child and adolescent psychiatrists were invited to join the Group as visiting experts for the discussion of the data. The advice of the group informed CSM s announcement on 10 June, that paroxetine was contraindicated in patients under the age of 18 with major depressive disorder. 

The efficacy of vitamin C supplementation as an adjunct to fluoxetine therapy for treating major depressive disorders in children has been evaluated in a six-month randomised, double-blind, placebo-controlled pilot study including 24 participants. No major adverse events were observed [313. 

Methylphenidate is a CNS stimulant similar to amphetamine however, in usual doses it has a more expressed action on mental activity rather than physical or motor activity. In therapeutic doses it does not raise blood pressure, respiratory rate, or increase heart rate. All of these effects as well as a number of others are associated with general excitement of the CNS. Tremor, tachycardia, hyperpyrexia, and a state of confusion can result from using large doses. It is used in treating moderate depression and apathetic conditions, and also as an adjuvant drug for treating attention deficit disorder in children.Synonyms of this dmg are meridil, ritalin, and others. 

Kaufman, J. (1991) Depressive disorders in maltreated children. / Am Acad Child Adolesc Psychiatry 30 257-265. 

Geller, D., Biederman, J., Faraone, S.V., Frazier, J., Coffey, B.J., Kim, G., and Bellordre, C.A. (2000) Clinical correlates of obsessive compulsive disorder in children and adolescents referred to specialized and non-specialized clinical settings [In Process Citation]. Depress Anxiety 11 163-168. 

Emslie, G.J., Rush, A.J., Weinberg, W.A., Gullion, C.M., Rintel-mann, J., and Hughes, C.W (1997a) Recurrence of major depressive disorder in hospitalized children and adolescents. / Am Acad Child Adolesc Psychiatry 36 785—792. 

Multiple studies have noted the comorbidity between PTSD and depressive disorders (Goenjian et ah, 1995), as well as between PTSD and externalizing disorders (Cuffe et ah, 1994 Glod and Teicher, 1996). Younger children with PTSD may present with classical features of attention-deficit hyperactivity disorder (ADHD), including hyperactivity, impulsivity, restlessness, irritability, and distractibility (Cuffe et ah, 1994 De Beilis and Putnam, 1994 McLeer et ah, 1994 Loof et al., 1995 De Beilis et ah, 1999). More serious externalizing disorders, such as conduct disorder (CD) and oppositional defiant disorder (ODD), are also commonly comorbid with PTSD (Arroyo and Eth, 1985 Steiner et al., 1997). Similarly, the relationship between PTSD and substance use disorders in children has been noted in several studies (Arroyo and Eth, 1985 Brent et al., 1995 Loof et al., 1995). 

The issues of whether depression is underdiagnosed, and more generally, whether the construct of depression is also applicable to children, have been discussed in both Europe (Rutter et ah, 1986) and the United States (Beardslee et ah, 1985). As in the DSM-IV, the ICD-10 has no specific category for depressive disorder in childhood, so diagnostic criteria developed for adult patients must be applied to children. However, a combination category for depression and conduct disorder is included in the ICD-10, depressive conduct disorder, for which the child must fulfill criteria for both depression and conduct disorder. 

Sertraline is manufactured by Pfizer under the name Zoloft, in three dosages 25,50, and 100 mg. Zoloft is prescribed for depression, obsessive-compulsive disorder, panic disorder, social anxiety disorder, and post-traumatic stress disorder. Sertraline is also used to treat obsessive-compulsive disorder in children. 

Before the idea of anxiety disorders in children was established, studies tended to focus on behaviors that suggested an anxiety disorder. Much research prior to 1980 investigated the effects of certain medications on children and teens who refused to go to school. This refusal could be rooted in several types of disorders, including phobia, social anxiety disorder, and depression. 

Although the usefulness of the atypical antipsychotics is best documented for the positive symptoms of schizophrenia, numerous studies are documenting the utility of these agents for the treatment of positive symptoms associated with several other disorders (discussed in Chapter 10 see Fig. 10—2). Atypical antipsychotics have become first-line acute and maintenance treatments for positive symptoms of psychosis, not only in schizophrenia but also in the acute manic and mixed manic-depressed phases of bipolar disorder in depressive psychosis and schizoaffective disorder in psychosis associated with behavioral disturbances in cognitive disorders such as Alzheimer s disease, Parkinson s disease, and other organic psychoses and in psychotic disorders in children and adolescents (Fig. 11—52, first-line treatments). In fact, current treatment standards have evolved in many countries so that atypical antipsychotics have largely replaced conventional antipsychotics for the treatment of positive psychotic symptoms except in a few specific clinical situations. 

The most important problem encountered with amphetamines is abuse and the development of dependence. The most rapid amfetamine epidemic occurred in Japan after World War II, where there had been little or no previous abuse (83). Although a high proportion of amfetamine users probably already have emotional and social difficulties, sustained abuse can result in serious psychiatric complications, ranging from severe personality disorders to chronic psychoses (84,85). Whereas signs of intense physical dependence are not thought to occur (SED-9, 9), withdrawal may be associated with intense depression (SED-9, 9) (86), and relapses in psychiatric disorders have often been noted. Some countries in which the problem became widespread banned amphetamines, and Australia restricted their use to narcolepsy and behavioral disorders in children. Amfetamine dependence developed into a serious problem in the USA (and to a lesser extent in the UK), where it followed the typical pattern of drug dependence (SED-9, 7,10). 

Dr. Lynn Crismon s work in developing the Texas Medication Algorithms for treatment of depression in children and adults and the treatment of attention-deficit hyperactivity disorder in children" "" laid the groundwork for psychiatric pharmacists to work with psychiatrists, psychologists, other health care professionals, and consumer groups to develop and implement national therapeutic guidelines. 

Although several antidepressants are EDA-approved for use in children, only one, fluoxetine, is currently approved for childhood depression. Imipramine is approved for the treatment of enuresis, clomipramine for obsessive-compulsive disorder in children 12 years and older, and fluvoxamine along with fluoxetine is approved for obsessive-compulsive disorder in children. The treatment of depression in children remains challenging, as depression can be difficult to diagnose and treat once identified. The studies involving imipramine, sertraline, and fluoxetine found that the dose range and titration as well as adverse effects were similar to those in adults. " ... 

Depression is one of the most common conditions in the UK, affecting one in five people at some stage in their life. The World Health Organization (WHO) estimates that by 2020 depression will be the biggest global health concern after chronic heart disease. Depression occurs in children, adolescents, women in menopause, the elderly, or those with mental disorder, especially in menopause. - The symptom of depression in menopause will cause mood obstacles about 10 years later. - ... 

The besylate salt of mesoridazine 43 is a commercially available antipsychotic medication that is used for treating schizophrenia and mania as well as major depression, anxiety, or severe behavior disorders in children. Mesoridazine 43 has four enantiomers, but the commercial samples are sold as only one diastereomeric pair. The methyl sulfoxide peak of 43 in the H NMR spectrum in the presence of 39 exhibits a peak for each of the four enantiomers. The areas of the sulfoxide resonances were used to compare the diastereomeric ratio of freshly prepared samples of 43 with commercial samples for changes in the ratio of the different isomers. ... 

Children of opiate addicts have been shown to have poorer social, educational and health status and to be at higher risk of abuse than their peers (Keen et al., 2000). However, given the high rates of psychiatric comorbidity (in particular, depression) in opiate-dependent patients (Brooner et al., 1997 Khantzian and Treece, 1985), it may be that some of the increased risk in children stems from this greater parental depression. Nunes et al. (1998) reported higher incidence of conduct disorder and global and social impairment for children of addicts with major depression compared to addicts without depression and controls, but not compared with children of depressed patients without substance use disorders. 

The dopamine transporter has been a target for developing pharmacotherapies for a number of CNS disorders including ADHD, stimulant abuse, depression and Parkinson s disease. Several excellent reviews in this area have been recently published [28-30]. The dopamine reuptake inhibitor methylphenidate has been successfully used for decades in the management of ADHD in children and adolescents. It remains a first-line treatment along with amphetamine for this disorder [31,32]. 

Suicidaiity in chiidren and adoiescents Antidepressants increased the risk of suicidal thinking and behavior (suicidaiity) in short-term studies in children and adolescents with major depressive disorder (MDD) and other psychiatric disorders. Anyone... 

Suicidality in children and adolescents Antidepressants increased the risk of suicidal thinking and behavior (suicidality) in short-term studies in children and adolescents with major depressive disorder (MDD) and other psychiatric disorders. Anyone considering the use of trazodone or any other antidepressant in a child or adolescent must balance this risk with the clinical need. Patients who are started on therapy should be observed closely for clinical worsening, suicidality, or unusual changes in behavior. Families and caregivers should be advised of the need for close observation and communication with the prescriber. Trazodone not approved for use in pediatric patients (see Clinical worsening and suicide risk and Children sections in Warnings). 

---