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Biomedical subjects

R W Lam

Publications and source records attributed to R W Lam.

At least 37 records · Page 2Linked to original sources
PubMed2000

Does the addition of pindolol accelerate the response to electroconvulsive therapy in patients with major depression? A double-blind, placebo-controlled pilot study.

There is evidence that addition of pindolol, a beta-adrenergic/5-hydroxytryptamine-1A antagonist, can accelerate the onset of action of antidepressant medications. The purpose of this study was to determine whether pindolol administration can induce a rapid improvement in depressive symptoms in patients receiving electroconvulsive therapy (ECT) within six ECT treatments. A total of 20 patients with DSM-IV-diagnosed major depression who were undergoing a course of ECT as the clinically indicated treatment were recruited. They were neuroleptic, lithium, and antidepressant free for at least 1 week before the study. Of the 20 patients, 9 patients had been randomly assigned to receive pindolol 2.5 mg three times daily, and 11 patients received identical placebo three times daily for the duration of the first 6 ECT treatments. One of 9 patients in the pindolol group and 4 of 11 patients in the placebo group dropped out of the study. Using an outcome measure of a score < or =12 on the 29-item Hamilton Rating Scale for Depression (HAM-D), the authors found that four (50%) of eight patients responded to the combination treatment of ECT and pindolol within six ECT treatments. In contrast, none (0%) of seven patients who received placebo responded to ECT treatment. Furthermore, both mean 29-item HAM-D and Clinical Global Impression Scale scores after the sixth ECT treatment were significantly lower in patients treated with pindolol compared with those treated with placebo. However, the number of total ECT treatments within a course or the overall efficacy of ECT treatment was not altered by the addition of pindolol. The results of this study suggest that within six ECT treatments, pindolol administration hastens antidepressant effects of ECT in some depressed patients.

Adrenergic beta-Antagonists↗
PubMed2000

Effects of light therapy on suicidal ideation in patients with winter depression.

BACKGROUND: Recent case reports suggest that some patients with seasonal affective disorder (SAD) may become suicidal after initial treatment with light therapy. This retrospective study sought to determine the effects of light therapy on suicidal ideation in patients with SAD. METHOD: The cases of 191 depressed patients with SAD by DSM-III-R or DSM-IV criteria treated with an open trial of morning light therapy using cool white fluorescent light boxes (2500 lux for 2 hours per day or 10,000 lux for 30 minutes per day) for 2 weeks were retrospectively analyzed. Patients had been rated before and after treatment with the expanded Hamilton Depression Rating Scale (SIGH-SAD). RESULTS: Sixty-seven percent of patients were rated as clinical responders to light therapy. There was significant improvement in the SIGH-SAD suicide item score, with 45% of patients showing a reduction in score. Only 6 patients (3%) had slight worsening of suicide scores. No patients attempted suicide or discontinued light therapy because of emergent suicidality. CONCLUSION: Light therapy relieves suicidal ideation in patients with SAD consistent with overall clinical improvement. Emergence of suicidal ideas or behaviors is very uncommon with light therapy.

Adult↗
PubMed2000

Pathophysiology of seasonal affective disorder: a review.

The study of the pathophysiology of seasonal affective disorder (SAD, also known as winter depression) has historically been intimately linked to investigations into the mechanisms of action of light therapy. This paper reviews the studies on the pathophysiology of SAD with emphasis on circadian, neurotransmitter, and genetic hypotheses. There is substantial evidence for circadian phase shift and serotonergic hypotheses, but conflicting results may indicate that SAD is a biologically heterogeneous condition. Recent progress in defining the molecular mechanisms of the human circadian clock and retinal phototransduction of light will provide important new directions for future studies of the etiology and pathophysiology of SAD.

Circadian Rhythm↗
PubMed1999

A controlled study of light therapy in women with late luteal phase dysphoric disorder.

Previous studies suggest that light therapy, as used to treat seasonal affective disorder, may be beneficial for pre-menstrual depressive disorders. We conducted a six-menstrual cycle randomized, double-blind, counter-balanced, crossover study of dim vs. bright light therapy in women with late luteal phase dysphoric disorder (LLPDD). Fourteen women who met DSM-III-R criteria for LLPDD completed two menstrual cycles of prospective baseline monitoring of pre-menstrual symptoms, followed by two cycles of each treatment. During the 2-week luteal phase of each treatment cycle, patients were randomized to receive 30 min of evening light therapy using: (1) 10000 lx cool-white fluorescent light (active condition); or (2) 500 lx red fluorescent light (placebo condition), administered by a light box at their homes. After two menstrual cycles of treatment, patients were immediately crossed over to the other condition for another two cycles. Outcome measures were assessed at the mid-follicular and luteal phases of each cycle. Results showed that the active bright white light condition significantly reduced depression and pre-menstrual tension scores during the symptomatic luteal phase, compared to baseline, while the placebo dim red light condition did not. These results suggest that bright light therapy is an effective treatment for LLPDD.

Adult↗
PubMed1999

Decrease in brain serotonin 2 receptor binding in patients with major depression following desipramine treatment: a positron emission tomography study with fluorine-18-labeled setoperone.

BACKGROUND: The neuroreceptor changes involved in therapeutic efficacy of various antidepressants remain unclear. Preclinical studies have shown that long-term administration of various antidepressants causes down-regulation of brain serotonin 2 (5-HT2) receptors in rodents, but it is unknown if similar changes occur following antidepressant treatment in depressed patients. Our purpose, therefore, was to assess the effects of treatment with desipramine hydrochloride on brain 5-HT2 receptors in depressed patients using positron emission tomography (PET) and fluorine-18 (18F)-labeled setoperone. METHODS: Eleven patients who met DSM-IV criteria for major depression as determined by a structured clinical interview for DSM-III-R diagnosis and suitable for treatment with desipramine were recruited. Ten patients underwent a PET scan before and another after 3 to 4 weeks of treatment with desipramine. RESULTS: Eight of the 10 patients responded to desipramine treatment as indicated by more than 50% decrease in Hamilton Depression Rating Scale scores. Depressed patients showed a significant decrease in 5-HT2 receptor binding as measured by setoperone binding in frontal, temporal, parietal, and occipital cortical regions following desipramine treatment. The decrease in 5-HT2 receptor binding was observed bilaterally and was particularly prominent in frontal cortex. CONCLUSIONS: Depressed patients showed a significant reduction in available 5-HT2 receptors in the brain following desipramine treatment, but it is unknown if this change in 5-HT2 receptors is due to clinical improvement or an effect of desipramine that is unrelated to clinical status.

Antidepressive Agents, Tricyclic↗
PubMed1999

Growth hormone response to baclofen in patients with mania: a pilot study.

RATIONALE: Growth hormone (GH) response to a challenge with a GABAB receptor agonist, baclofen, is considered to provide an in vivo index of hypothalamic GABAB receptor function in humans. OBJECTIVES: The purpose of this study was to explore the role of GABAB receptors in the pathophysiology of mania by measuring plasma GH response to baclofen in ten manic patients and ten matched healthy controls. METHODS: After obtaining blood samples for baseline GH levels, a single dose of 20 mg baclofen was administered orally to all the subjects, and further blood samples were obtained at 30-min intervals for the following 3 h. RESULTS: We found that baclofen administration led to a significant increase in GH release both in manic patients and healthy controls, but the GH response to baclofen in manic patients was significantly enhanced when compared to healthy controls. CONCLUSIONS: Our results suggest that manic patients may have an up-regulated hypothalamic GABAB receptor function. However, in light of the limitations including small sample size and absence of placebo control, our results should be viewed as preliminary. Further studies with a larger number of manic patients and a placebo control design are needed to replicate our finding before any firm conclusion can be drawn.

Acute Disease↗
PubMed1999

Hypothermic, ACTH, and cortisol responses to ipsapirone in patients with mania and healthy controls.

BACKGROUND: The selective 5-HT1A receptor agonist ipsapirone causes dose-dependent decrease in body temperature and increase in adrenocorticotropic hormone (ACTH) and cortisol release in humans. These responses are attenuated by 5-HT1A receptor antagonists, suggesting that hypothermia, ACTH and cortisol release induced by ipsapirone are indeed mediated by 5-HT1A receptors and that these responses provide a valid index of 5-HT1A receptor function in humans. METHODS: To examine the 5-HT1A receptor sensitivity in patients with mania, we studied six manic patients and six age and sex matched healthy controls. After obtaining a blood sample for baseline hormone levels and measuring body temperature, a single dose of 0.3 mg/kg of ipsapirone was given orally to all the subjects and further bloods and temperature reading were obtained every 30 minutes for 3 hours. RESULTS: We found that ACTH and cortisol responses to ipsapirone were significantly increased in mania when compared to healthy controls, but there was no significant difference in hypothermic response to ipsapirone between the two groups. LIMITATIONS: A lack of placebo control, heterogeneity of patients, and a small sample size are the limitations. CONCLUSIONS: Our findings suggest that manic patients may have enhanced postsynaptic 5-HT1A receptor sensitivity, but presynaptic 5-HT1A receptors are unaltered in this condition. Further placebo-controlled studies with a larger number of manic patients are needed to verify this.

Administration, Oral↗
PubMed1999

Growth hormone response to baclofen in patients with seasonal affective disorder: effects of light therapy.

There is evidence for gamma-aminobutyric acid (GABA) dysfunction in the pathophysiology and treatment response of patients with major depression, but this has not been studied in seasonal affective disorder (SAD). Growth hormone (GH) response to a challenge with a GABAB receptor agonist, baclofen, is considered an in vivo index of hypothalamic GABAB receptor function in humans. To explore the role of GABAB receptor function in SAD, we compared the GH response to baclofen challenge in 15 patients with SAD and 20 matched healthy controls. Of the 15 patients with SAD, 14 had repeat baclofen challenge following 2-week treatment with light therapy. The results showed that baclofen administration led to a significant increase in GH release both in patients with SAD and normal controls. There was no significant difference in the GH response to baclofen between the two groups. Furthermore, 2-week treatment with light therapy did not significantly alter the baclofen-induced GH response in patients with SAD, in spite of a clear therapeutic effect. The results of this study suggest that hypothalamic GABAB receptor function, as measured by baclofen induced GH release, is not altered in patients with SAD or by light therapy.

Adult↗
PubMed1999

Clinical predictors of short-term outcome in electroconvulsive therapy.

OBJECTIVES: Electroconvulsive therapy (ECT) remains one of the most effective biological treatments for major depression. However, there is little information on the clinical use of ECT, and most studies were conducted before the introduction of newer antidepressants and before improvements in ECT delivery. This study examined ECT use in a university teaching hospital to determine predictors of short-term ECT outcome. METHODS: This was a retrospective chart review of ECT over the period 1994-1996. Data extracted from the chart included demographic information, clinical features of depression, and documented antidepressant trials. Outcome measures, based on the chart notes, included Clinical Global Impression (CGI) and cognitive side effects of ECT at 1 week post-ECT or at discharge if sooner. RESULTS: Of 174 patients who received ECT, 130 had a diagnosis of unipolar major depressive disorder. Of these 130 patients, 92% were refractory to at least 1 antidepressant medication. After a clinical course of ECT, 87% were rated as "much" or "very much" improved on the CGI. Moderate side effects were noted in 16% of patients, while only 7% had marked side effects. Medication resistance was not related to ECT response. No significant clinical predictors (symptoms, chronicity, number of antidepressant trials) of ECT outcome were found on a stepwise multiple-regression analysis. CONCLUSIONS: These results support previous studies showing that ECT results in very good short-term response in major depressive disorder and that the cognitive side effects of ECT are reasonable. Despite the limitations of this study (retrospective, chart review, global measures), the results will inform clinicians who are recommending ECT for their patients.

Adult↗
PubMed1998

Seasonal mood change and personality: an investigation of genetic co-morbidity.

Clinical observations and empirical studies suggest that Seasonal Affective Disorder (SAD) is related to personality. The present study estimates the genetic and environmental correlations between the Global Seasonality Score (GSS) from the Seasonal Pattern Assessment Questionnaire and personality measures, assessed using the NEO Five Factor Inventory (NEO-FFI) and the Dimensional Assessment of Personality Pathology (DAPP) in a volunteer sample of 163 monozygotic (MZ) pairs (102 female and 61 male pairs) and 134 dizygotic (DZ) pairs (70 female, 38 male and 26 opposite-sex pairs). Large genetic correlations were found between the GSS and NEO-FFI Neuroticism (0.52: 95% CI = 0.36-0.71) and DAPP-BQ Cognitive Dysregulation (0.50: 95% CI = 0.30-0.71), Affective Lability (0.49: 95% CI = 0.29-0.77), Anxiousness (0.37: 95% CI = 0.18-0.55) and Stimulus Seeking (0.45: 95% CI = 0.25-0.64) scales. The genetic correlations with the remaining scales, such as Extraversion (0.06: 95% CI = -0.16-0.26), Compulsivity (-0.09: 95% CI = -0.31-0.12) and Submissiveness (0.15: 95% CI = -0.05-0.34) were uniformly small. All environmental correlations between the GSS and personality scales were < or = 0.19. These results provide evidence that the observed correlations between these seasonality and personality dimensions are attributable to common genetic factors and that environmental influences are domain specific.

Adolescent↗
PubMed1998

Effects of lamotrigine on the 5-HT1A receptor function in healthy human males.

BACKGROUND: Lamotrigine, a new anticonvulsant, has recently been reported to be effective in treating patients with bipolar mania, depression, and schizoaffective disorder, suggesting that it is perhaps a mood stabilizer with antimanic and antidepressant properties. However, the mechanism of action underlying its efficacy in mood disorders is still unknown. METHODS: To explore the role of 5-HT1A receptors in the mechanism of action of lamotrigine, we measured the body temperature and plasma cortisol responses to a challenge with a selective 5-HT1A receptor agonist ipsapirone in ten healthy human males. Each subject received 0.3 mg/kg of ipsapirone hydrochloride tablets at time "0". Body temperature readings and blood samples for cortisol levels were obtained at 0, 30, 60, 90, 120, 150, 180 min. The ipsapirone challenge tests were repeated after 1 week treatment with lamotrigine (100 mg/day). RESULTS: Treatment with lamotrigine for 1 week did not significantly alter the hypothermic or cortisol responses to ipsapirone. LIMITATIONS: The limitations of this study included small sample size, low treatment dose, short treatment interval, and lack of placebo control. CONCLUSIONS: Our findings might suggest that 5-HT1A receptor function is not involved in the mechanism of action of lamotrigine in humans. Further placebo-controlled studies with a higher lamotrigine dose and a longer treatment interval in a larger number of subjects are needed to verify this.

Adult↗
PubMed1998

Divalproex sodium attenuates growth hormone response to baclofen in healthy human males.

The effect of divalproex sodium (DVP) on gamma-aminobutyric acid-B (GABAB) receptor function in humans was assessed by measuring growth hormone (GH) responses to a challenge with a GABAB receptor agonist, baclofen, in 10 male healthy volunteers. Each subject received 20 mg of baclofen at 10:00 A.M., and blood samples were collected for measuring GH before and 30, 60, 90, 120, 150, 180 min after baclofen administration. The baclofen challenge test was repeated after 1 week of treatment with DVP (1000 mg/day). The results showed that the plasma GH response to baclofen was significantly attenuated by the DVP treatment and that the degree of attenuation was positively correlated with the blood levels of valproic acid. Our findings suggest that DVP downregulates hypothalamic GABAB receptor function in humans.

Adult↗
PubMed1998

Cortisol, hypothermic, and behavioral responses to ipsapirone in patients with bipolar depression and normal controls.

To examine if 5-HT1A receptor function is involved in the pathophysiology of bipolar depression, we measured the cortisol, hypothermic and behavioral responses to ipsapirone, a 5-HT1A receptor agonist, in 8 patients with bipolar depression and 26 normal controls. After obtaining blood samples for baseline cortisol levels and measuring baseline body temperature, a single dose of 0.3 mg/kg of ipsapirone was administered orally to all the subjects, and further blood and temperature readings were obtained every 30 min for 3 h. The results showed that the administration of ipsapirone led to a significant increase in cortisol release and a significant decrease in body temperature both in bipolar depressed patients and normal controls. There was no significant difference in the cortisol or hypothermic responses to ipsapirone between groups. However, there was a significant positive correlation between the Hamilton Depression Rating (HAMD) scores and the hypothermic response in the depressed patients, while the HAMD scores were not significantly correlated with the cortisol response. Comparing our findings with those of previous studies, we suggest that the alterations in 5-HT1A receptor sensitivity in depressed patients may be related to the severity of depression, and they may only occur in more severely depressed patients.

Adult↗
PubMed1998

A community-based clinic survey of antidepressant use in persons with schizophrenia.

OBJECTIVE: To determine the rates of antidepressant and antipsychotic use in the treatment of schizophrenia. METHOD: The primary therapists at 8 community mental health centres in a metropolitan Canadian city completed a survey questionnaire for all of their active clients. Information was collected about diagnoses, medication treatments, and clinical variables. RESULTS: There were 3555 clients, 1552 (43.7%) of which had a diagnosis of schizophrenia. Of clients with schizophrenia, 94% were prescribed antipsychotic medications, and 11.6% of these were also prescribed antidepressant medications. There were differences between the combination-treatment group and the antipsychotic-alone group in gender ratio, rates of concurrent diagnoses of mood disorder, level of current functioning, and total number of hospitalizations. CONCLUSION: In this community-based sample of clients with schizophrenia, antidepressants and antipsychotics are commonly prescribed in combination, even though the rate of concurrent mood disorders diagnoses is low. Further studies should clarify the efficacy and indications for antidepressant use in this population.

Antidepressive Agents↗
PubMed1997

Growth hormone response to sumatriptan (5-HT1D agonist) challenge in seasonal affective disorder: effects of light therapy.

To explore the role of serotonergic system in seasonal affective disorder (SAD), we compared growth hormone (GH) responses to a challenge with a novel 5-HT1D receptor agonist sumatriptan between 11 patients with SAD and nine healthy controls. Of the 11 patients with SAD, nine had repeat sumatriptan challenge following treatment with light therapy. The results showed that GH responses were significantly blunted during winter depression in patients with SAD compared to healthy controls. The GH responses normalized following treatment with light therapy to similar levels in controls. The results of this study provide a support for the role of serotonergic system in pathophysiology of SAD and in the mechanism of action of light therapy.

Adult↗