Fluoxetine and methylphenidate in combination for treatment of attention deficit disorder and comorbid depressive disorder.

ABSTRACT Children and adolescents with attention deficit disorders (usually with comorbid conditions), who had shown inadequate therapeutic responses to methylphenidate, were treated by the addition of fluoxetine to methylphenidate. After 8 weeks in open trial, all 32 patients showed positive therapeutic responses in attention, behavior, and affect. Thirty of the 32 children showed clinically significant responses and the other two had statistically but not clinically significant responses. After 12 weeks of treatment, one patient showed a deterioration in clinical status. The children had improved report card grades in major academic subjects {p < 0.0001), and showed significant improvements (p < 0.0001) on the Children's Global Assessment Scale (C-GAS), Conners Parents Rating Scales (CPRS), and Children's Depression Inventory (CDI). Children who initially appeared more impaired on the C-GAS, CDI, CPRS, and GPA showed more improvement on the combined regimen. No significant side effects were observed, using a gradual elevation of fluoxetine dosage. About 40% of the patients showed substantial clinical effects with doses of fluoxetine below 20 mg daily. These preliminary results suggest that fluoxetine and methylphenidate in combination may be safe and effective for some children with attention-deficit hyperactivity disorder (and with comorbid anxiety or depressive symptoms) who do not show adequate responses to methylphenidate or fluoxetine alone.

Delusional depression and bipolar spectrum: evidence for a possible association from a family study of children.

Recent pedigree studies demonstrating a possible linkage of bipolar disorder to markers on different chromosomes have included family members with major depression and cyclothymia as affected. There is general agreement that cyclothymia is related to bipolar disorder and that major depression is heterogenous. It is unclear which subtype of major depression is related to bipolar disorder. Data suggesting a relationship between delusional subtype of major depression and bipolar spectrum are presented. The data derive from a direct-interview study of 220 offspring (ages 6 to 23 years) of probands with either delusional or nondelusional major depression and normal controls. The children of delusional as contrasted with nondelusional probands had nearly a threefold increase in cyclothymia, were more often described by health professionals as hyperactive, and had increased school and social impairments. These findings in children replicate earlier findings in adults on the possible relationship between delusional depression and bipolar disorder and its spectrum. The findings must be considered tentative, however, because of the small sample of children in the subgroups of interest.

Parent and child reports of depressive symptoms in children at low and high risk of depression.

The K-SADS-E psychiatric interview was administered to children and parents (N = 220) from families containing proband parents who had previously been depressed or who were normal. Agreement between parents and their children about depressive symptoms in the children was significant but low. Boy's reports agreed more highly with their parents' reports about them than did girls' reports. Overall, the children reported more depressive symptoms than their parents reported about them and the overall pattern suggests that parents are relatively insensitive to their children's depressive symptomatology, but their reports show high specificity. The implications of these findings for research and clinical work are discussed.

Children of depressed parents. Increased psychopathology and early onset of major depression.

Data on the psychiatric diagnosis, overall functioning, and treatment of 220 6- to 23-year-old subjects who were at high or low risk for major depression are presented. The subjects' diagnoses were made by a child psychiatrist based on best-estimate evaluation of diagnostic information derived from structured interviews (Schedule for Affective Disorders and Schizophrenia for School-Aged Children, Epidemiologic Version) with the subjects and separately with their mothers about their children. The major findings were an increased overall prevalence of major depression and substance abuse, psychiatric treatment, poor social functioning, and school problems in the children of depressed proband parents compared with children of normal proband parents. Overall prepubertal depression was uncommon and the sex ratios were equal. After 12 years of age, there was an increasing preponderance of female subjects in the group with major depression. The mean age at onset of major depression was similar for male and female subjects. However, it was significantly earlier in the children of depressed probands (mean age at onset, 12 to 13 years) compared with the children of normal probands (mean age at onset, 16 to 17 years). Symptom profiles and additional types of diagnoses in the depressed children from either proband parent group did not differ. These children are being followed up longitudinally to determine the prognostic significance, persistence, recurrence, and recall of their symptoms. Several research and clinical strategies are suggested by these data.

Assessing psychiatric disorders in children. Discrepancies between mothers' and children's reports.

Results were compared from independent interviews using the Schedule for Affective Disorders and Schizophrenia for School-aged Children-Epidemiologic Version and DSM-III with 220 subjects (ages 6 to 23 years) and their parent informants. In agreement with results from studies using a variety of structured diagnostic interviews or symptom scales, considerable discrepancies were found between parents' and children's reports on the degree and nature of the child's psychopathology. The children reported more illness about themselves than their parents reported about them. The parents' reports were primarily a subset of the children's reports. Various factors that might affect agreement, including demography, parental clinical status, severity of illness, and treatment, were also explored. The findings that parents under-report psychiatric disorders in their children are comparable with those reported in studies of adults when family informants are used to obtain diagnostic information. Until these parent-child discrepancies can be resolved by longitudinal, family, and other research, diagnostic assessment of children should include direct interviews with them. An independent assessment of the child's diagnosis based on information from multiple informants, including the child, may be the best estimate.

Depressed parents and their children. General health, social, and psychiatric problems.

Two hundred twenty children (aged 6 to 23 years) from families with either depressed or normal (nonpsychiatrically ill) parents of comparable sociodemographic backgrounds were studied. The children from families in which at least one parent had experienced a major depression were reported to have had more adverse perinatal events; were later in achieving some developmental landmarks; had more convulsions, head injuries, operations, and psychiatric disorders (particularly major depression); and made more suicide attempts. Overall, there were no significant differences in IQ between children in both groups. Mothers in families with a depressed parent reported more medical problems during pregnancy and labor, and the children were reported to have experienced more distress at birth. Since major depression is a highly prevalent disorder in women of childbearing ages, these findings have direct clinical implications for pediatricians. Their specificity for major depression, as contrasted with other psychiatric disorders or chronic illnesses in the parents, requires further study.

Onset of major depression in early adulthood. Increased familial loading and specificity.

In a family study of 133 probands with major depression and 82 normal control subjects, and 1,518 of their first-degree relatives, we found a substantial inverse relationship between the age of onset of major depression in the probands and the risk of major depression in their relatives. The relatives of probands whose onset of major depression occurred when they were younger than 20 years of age had the highest risk of major depression, compared with the relatives of probands who had later ages of onset or with the relatives of normal subjects. Probands with an age of onset of 40 years or more had familial loading that was only slightly higher than the families of normal control subjects. Our statistical methods enabled us to examine the relationship of the ages of onset in the probands and their relatives while accounting for possible confounding factors. More studies will be needed to sort out secular changes in the rates of the occurrence of major depression among young persons (cohort effect) from the high familial loading of major depression that has its onset in childhood and adolescence, and to determine whether the specificity of transmission of early-onset depression is the result of a single homogeneous disorder.

Depression and anxiety disorders in parents and children. Results from the Yale family study.

The children (aged 6 to 17 years) of probands with primary major depression, with and without various anxiety disorders, were compared with the children of a matched normal control group. The results from the study of these young children parallel our previous findings among the adult first-degree relatives of these probands. Depression in the proband increased the risk of depression in the children. Depression plus panic disorder or agoraphobia in the proband conferred an additional risk of depression and of an anxiety disorder in the children. Panic disorder in the parents conferred more than a threefold increased risk of separation anxiety in the children. Other factors that increased the risk to children were degree of familial loading for psychiatric illness, parental assortative mating, and parental recurrent depression. The findings suggest a relationship between depression and some of the anxiety disorders, and between adult panic disorder and agoraphobia and transmission of anxiety disorders to children.

A case of akinesia induced by amoxapine.

A depressed woman who was treated with amoxapine developed akinesia, which was mistaken for depression. This extrapyramidal syndrome has not previously been linked with this widely used antidepressant, and clinicians should be aware of the association.

Use of a structured diagnostic interview to identify bipolar disorder in adolescent inpatients: frequency and manifestations of the disorder.

The authors interviewed 17 adolescent inpatients and their mothers with the Schedule for Affective Disorders and Schizophrenia for School-Aged Children and Adolescents, Epidemiological Version (K-SADS-E), a semistructured interview that generates RDC and DSM-III diagnoses for major affective disorders and nonaffective psychoses and DSM-III diagnoses for dysthymic, cyclothymic, and other selected disorders. Five of the patients (29%) satisfied DSM-III criteria for bipolar disorder or atypical bipolar (bipolar II) disorder, although these diagnoses had not been identified in the hospital charts. These data support previous findings that bipolar disorder occurs moderately frequently in adolescent inpatients, although it is often unrecognized. Moreover, the disorder can be readily identified with structured diagnostic methods.