northiaden and Depressive-Disorder

This study looks at the outcome of infants exposed to dothiepin in breast milk in an attempt to guide clinicians on the risk-benefit ratio of breast-feeding when on antidepressants.. Thirty women, who had had HDRS scores > 15 within the first five years postpartum from the same women's hospital, were assessed with their children 3-5 years postpartum; half had breast-fed while on dothiepin (study group). Thirty-six non-depressed women were also assessed. Rating scales assessed depression, anxiety, self-esteem, personality, social support, marital relationship, child behaviour and temperament. The children were assessed by the McCarthy Scale.. Comparisons of the two depressed groups showed no significant differences on any measures except marital conflict and child behaviour, which were the most disturbed in the study group (P < 0.001). Overall cognitive scores for the children did not differ between the groups. Higher levels of dothiepin and northiaden were associated with higher cognitive scores on subscales (P = 0.02).. We are cautiously optimistic about the lack of any negative associations between cognitive development and exposure to dothiepin via breast milk.

Topics: Antidepressive Agents, Tricyclic; Breast Feeding; Child Development; Child, Preschool; Depressive Disorder; Dose-Response Relationship, Drug; Dothiepin; Female; Follow-Up Studies; Humans; Infant; Male; Personality Assessment; Personality Development; Puerperal Disorders; Risk Factors

Ten patients suffering from primary depressive illness were treated with 150 mg/d of dothiepin for 4 weeks. Blood and plasma concentrations of dothiepin and two metabolites, dothiepin S-oxide and northiaden were measured by gas chromatography-mass spectrometry. Severity of depression was assessed using the Hamilton Depression Rating Scale. No significant correlation was found between amelioration score or percentage change and either blood or plasma concentrations of dothiepin, its metabolites or total drug and metabolite concentrations at week 4.

Topics: Adult; Aged; Depressive Disorder; Dibenzothiepins; Dothiepin; Female; Humans; Male; Middle Aged

The affinities of dothiepin and its principal metabolites northiaden, dothiepin sulphoxide and northiaden sulphoxide for [3H]imipramine binding sites in the rat cortical homogenates, and for [3H]spiperone and [3H]serotonin receptor sites in preparations from the rat frontal cortex and hippocampus were studied. As inhibitors of [3H]imipramine binding, the strengths of the drugs are, in terms of their IC50 (concentration corresponding to 50% inhibition): dothiepin 2.8 X 10(-6) M, northiaden 5.0 X 10(-6) M, northiaden sulphoxide 4.0 X 10(-5) M and dothiepin sulphoxide 3.2 X 10(-5) M. The potencies of the drugs in inhibiting serotonergic binding followed a similar trend. Using frontal cortical tissue suspensions and [3H]spiperone, the IC50 values were determined to be: dothiepin 4.2 X 10(-6) M, northiaden 5.0 X 10(-6) M, northiaden sulphoxide 1.6 X 10(-4) M and dothiepin sulphoxide 1.6 X 10(-4) M; whereas in hippocampal suspensions and using [3H]serotonin, the IC50 values were 2.5 X 10(-6) M, northiaden 4.0 X 10(-5) M, dothiepin sulphoxide 2.5 X 10(-4) M and northiaden sulphoxide greater than 10(-3) M. The influence of the drugs on the uptake of [14C]serotonin into human platelets was also investigated. All had an inhibitory effect upon the uptake, the order of potency being dothiepin greater than northiaden greater than northiaden sulphoxide greater than dothiepin sulphoxide. Plots of 1/v versus 1/s showed that the inhibition was competitive for all four compounds.

Topics: Animals; Binding, Competitive; Blood Platelets; Carrier Proteins; Cerebral Cortex; Depressive Disorder; Dibenzothiepins; Dothiepin; Hippocampus; Humans; Imipramine; Rats; Rats, Inbred Lew; Receptors, Drug; Receptors, Serotonin; Serotonin; Spiperone