Predicting response to antidepressant medication has been a challenge to clinicians and researchers for decades. Attention has been paid to the role of motor retardation as a putative indicator of treatment response, yet previous findings have been mixed. One reason for this inconsistency may be related to the subjective nature of motor retardation and how it is assessed. In the present study, we adopted a measure of motor programming previously shown to characterize parkinsonian bradykinesia to test whether neuromotor function could predict response to antidepressant treatment. Twenty-eight patients (14 males and 14 females with a mean age of 42.0 years) meeting DSM-IV criteria for a depressive disorder were randomized to receive 8 weeks of treatment with one of three antidepressant medications (sertraline, phenelzine, or bupropion). Treatment outcomes were assessed using the 17-item version of the Hamilton Rating Scale for Depression (HRSD). Patients were considered asymptomatic if their post-treatment HRSD total score was equal to or less than 7. Treatment responders (n=15) had significantly less baseline impairment (P=0.01) on the neuromotor measure than non-responders (n=13). There was a significant relationship between amount of improvement on the HRSD and severity of baseline neuromotor function (r=−0.51; P=0.006). No significant group effects were found for baseline psychomotor slowing or clinical ratings of motor retardation. These results demonstrate that a quantitative measure of motor programming may be a useful predictor of antidepressant non-response.

Background: The relationship between cigarette smoking and mood has received increasing attention. This retrospective study evaluated the relationship between mood disturbance and cigarette smoking status among patients with a current mood disorder. The association between level of nicotine dependence and severity of mood disturbance was also evaluated among current smokers.Method: Retrospective data for 252 patients (63.5% male, 85.0% white) admitted for treatment of a mood disorder at the San Diego Veteran Affairs Mental Health Clinical Research Center between November 1988 and June 1997 were studied. Ail current cigarette smokers at admission (N = 126) were matched with nonsmokers (N = 126) on the primary DSM-IV Axis I mood disorder diagnosis, admission status (inpatient or outpatient), gender age (+/- 5 years). and ethnicity. The Hamilton Rating Scale for Depression (HAM-D), the Beck Depression Inventory, and the Profile of Mood States (POMS) were administered to patients on admission. Conditional logistic regression analysis for matched sets with a backward elimination was used to identify factors independently predictive of current smoking status.Results: A greater number of cups of coffee consumed per day (p = .002), a history of alcohol ism (P = .004), and higher POMS fatigue subscale scores (p = .007) were predictive of current smoking status. Among current smokers, the HAM-D terminal insomnia item was positively associated with mean number of cigarettes smoked per day (p = .012).Conclusion: Cigarette smoking should be addressed in the treatment of patients with a current mood disorder. Smokers experience greater levels of fatigue than nonsmokers. In addition, higher cigarette consumption levels are associated with mild-to-severe symptoms of terminal insomnia.

Background: In previous studies, depletion of brain serotonin by administration of a tryptophan-free amino acid drink (TFD) (1) temporarily reversed the antidepressant effects of selective serotonin reuptake inhibitors (SSRIs) in euthymic patients who had a history of major depression, and (2) enhanced rapid eye movement (REM) sleep in normal volunteers. In this study, we hypothesized that the TFD would not only increase depressive symptoms but also the propensity for REM sleep in euthymic patients treated with SSRIs.Methods: Ten fully remitted, medicated male patients who had a history of major depressive episode ingested a 100-g TFD (the experimental dose) or a 25-g TFD (designed to be the control drink) in double-blind, random order on separate days. The effects were assessed with mood ratings, plasma tryptophan concentrations, and an all-night sleep electroencephalogram.Results: The TFDs produced a dose-dependent reduction in plasma tryptophan concentrations, sleep latency, and REM latency, as well as increased REM percentage, REM minutes, REM density, and total sleep time. Neither strength of TFD altered mood to a clinically significant degree.Conclusions: Although the TFD affected plasma tryptophan concentrations and various sleep measures, our study did not confirm previous reports that TFD temporarily reversed the antidepressant effects of SSRIs in euthymic patients. Our patients however, had been treated for a longer period with SSRIs and were more fully remitted at the time of the study. Our results suggest that TFD-induced relapse in SSRI-treated patients in remission decreases as a function of treatment duration, degree of remission, or both.

Background: Serotonin has been implicated in the regulation of sleep and mood. In animals a tryptophan-free amino acid drink (TFD) challenge has been found to reduce brain serotonin. We hypothesized this TFD would produce alterations in electroencephalographic (EEG) sleep commonly associated with depression, i.e., an enhancement of rapid eye movement (REM) sleep, and adversely affect mood ratings in humans. Methods: We investigated the effects of a TFD challenge in 11 healthy male subjects on EEG sleep and mood (assessed by Profile of Mood States). All subjects received on separate occasions an experimental drink containing approximately 100 g of an amino acid mixture (100% TFD) and a control drink containing one fourth strength (25% TFD) of the experimental drink 5 hours prior to sleep (6:00 pm). Results: Both drinks significantly decreased plasma tryptophan levels 5 hours postchallenge (11:00 pm). Both drinks significantly decreased REM latency, and the 25% TFD also increased REM time and REM% compared to baseline. No significant changes were found in subjective ratings of depression; however, subjects reported confusion and tension and a decrease in elation, vigor, and friendliness compared with baseline. Conclusions: These TFD findings further support the involvement of serotonin deficiency in EEG sleep findings commonly seen in depression.

To determine whether ipsapirone, a 5-HT1A agonist, differentially suppresses REM sleep in depressed patients compared with normal controls, we administered placebo, ipsapirone 10 mg, or ipsapirone 20 mg in a double-blind, random order before bedtime in 18 unmedicated patients with depression and 16 age-matched, gender-matched normal controls. Compared to placebo, ipsapirone affected REM sleep measures equally in depressed patients and controls as follows: (1) increased REM latency; (2) reduced total REM percent, REM time, and REM density; and (3) delayed the onset of REM sleep. In addition, ipsapirone had similar effects in patients and controls in other sleep measures: (1) reduced total sleep time; (2) delayed sleep onset time; and (3) increased sleep latency, stage 1%, stage 2%, the amount of stage 3 & 4 sleep in the first non-REM period, and wake time after sleep onset. The study does not support the hypothesis that downregulated 5-HT1A receptors mediate the pathophysiology or sleep disturbances of depression, although further studies are needed as these patients did not differ from controls in baseline sleep measures.

Depression may result from an increased ratio of cholinergic to aminergic central neurotransmission. The effect of centrally active anticholinergic agents on depressive ratings in depressed patients, however, has not been well studied. In a previous open label 4-week clinical trial, Kasper et al. (1981) reported that biperiden (Akineton) had antidepressant effects in depressed patients. We compared the effects of placebo and biperiden in a randomized, double-blind, parallel-design 6-week study. All patients received placebo for the first week and then received either biperiden (≤ 12 mg/day) or a peripherally acting anticholinergic agent, glycopyrrolate (Robinul, 1 mg/day) for 4 weeks. All patients received placebo during week 6. Both groups significantly improved, but biperiden did not demonstrate any significant benefit compared with glycopyrrolate. In a subgroup of patients receiving biperiden, the percentage of rapid eye movement sleep was significantly decreased only in the first week of biperiden compared with the initial placebo week, suggesting that tolerance to the central effects of biperiden developed. Further studies would be needed to determine whether anticholinergic agents possess antidepressant properties.

Caffeine, 10 mg/kg, was administered to 13 schizophrenic patients in a double-blind placebo-controlled study of its behavioral effects. Some measures of psychopathology were significantly increased: Brief Psychiatric Rating Scale (BPRS) total, BPRS subscales thought disorder, unusual thought content, and euphiria-activation, and several individual BPRS items. Nurses' Bunney-Hamberg ratings of psychosis and mania, comparing the day before with the day after pharmacological challenge, increased significantly. Compared to placebo, caffeine also produced significant increases of diastolic blood pressure and cortisol. Thus, these findings indicate that caffeine increases arousal and has a psychotogenic effect when administered to schizophrenic patients. The possible roles of various neurotransmitters is discussed with special emphasis on caffeine's actions on dopaminergic and adenosinergic systems.