ABSTRACT
Abnormal movements occur rarely with selective serotonin reuptake inhibitors (SSRIs). This report describes four consecutive autistic children who developed extrapyramidal side effects (EPS) following SSRI exposure. Videotapes, physician notes, and parental interviews were used retrospectively to rate symptoms on the Extrapyramidal Symptom Rating Scale. Findings suggest that EPS is a potential complication of SSRI treatment in autistic children.
Subject(s)
Autistic Disorder/drug therapy , Dyskinesia, Drug-Induced/diagnosis , Selective Serotonin Reuptake Inhibitors/adverse effects , Autistic Disorder/psychology , Basal Ganglia Diseases/chemically induced , Basal Ganglia Diseases/psychology , Child , Dyskinesia, Drug-Induced/psychology , Humans , MaleABSTRACT
Selective serotonin reuptake inhibitor (SSRI) augmentation with the 5-HT1A antagonist pindolol has met with mixed results. Recent studies using positron emission tomography (PET) suggest that pindolol doses used in these studies were too low to effect 5-HT1A autoreceptor blockade. To test the hypothesis that a single higher dose of pindolol would effectively augment antidepressant responses in SSRI-refractory patients, nine subjects with major depression unresponsive to paroxetine 40 mg/day given for 2 months or more were randomized to AM pindolol 7.5 mg (n=4) or placebo (n=5). Subjects were administered the Hamilton Depression Scale (HAM-D), the Hamilton Anxiety Scale (HAM-A), the Bech-Rafaelsen Melancholia Scale, and the Zung Depression Inventory at baseline and weeks 1, 2, 3, and 4. Subjects receiving pindolol exhibited significant improvements in all ratings beginning at week 2 which continued through week 4. Aside from transient dizziness and a five-point decrease in systolic/diastolic blood pressure associated with pindolol, no adverse effects were reported. Although results must be verified in a larger sample, these findings support previous studies indicating that pindolol can accelerate antidepressant responses during SSRI therapy. In addition, results reported here suggest that a single high dose of pindolol (7.5 mg) is a more effective augmentation strategy in SSRI-refractory patients compared with the same total dose given at 2.5 mg tid.
Subject(s)
Depressive Disorder, Major/drug therapy , Pindolol/therapeutic use , Serotonin Antagonists/therapeutic use , Adult , Depressive Disorder, Major/diagnosis , Drug Administration Schedule , Female , Humans , Male , Pindolol/administration & dosage , Serotonin Antagonists/administration & dosage , Severity of Illness Index , Surveys and QuestionnairesSubject(s)
Autistic Disorder/epidemiology , Autistic Disorder/metabolism , Serotonin/metabolism , Autistic Disorder/psychology , Case-Control Studies , Child , Child, Preschool , Family , Humans , Mental Disorders/psychology , Mood Disorders/epidemiology , Mood Disorders/metabolism , Receptors, Serotonin/metabolism , Social Environment , Surveys and QuestionnairesABSTRACT
Adenosine plays a key role in the regulation of tissue oxygenation, neuronal firing, and neurotransmitter release. Four receptor subtypes have been identified and cloned: A(1), A(2A), A(2B), and A(3), although only A(1) and A(2A) receptors are prominent in rat brain. Much evidence now indicates that A(2A) receptors (A(2A)R) are highly enriched within striatal medium-sized spiny GABAergic neurons where they are closely associated with, and modulate, D(2)-dopaminergic receptors involved in motor control and reward behaviors. There is also consensus that A(2A)R are present in the nucleus accumbens and olfactory tubercle where they have been postulated to interact with prostaglandins in the regulation of sleep. There is less agreement as to whether or not A(2A)R are present in other brain regions. The present study describes an autoradiographic procedure that utilizes [(3)H]ZM-241385 (4-(2-[7-amino-2-(2-furyl)[1,2,4]triazolo[2,3-alpha][1,3,5]triazin-5-ylamino]ethyl)phenol), a highly selective A(2A)-receptor ligand. Saturable specific binding was found in the rat caudate putamen with a K(d)=1.1 nM and B(max)=1150 fmol/mg. Binding was also found in the nucleus accumbens and the olfactory tubercle, but was not detected in extra-striatal brain regions.
