Platelet 3H-imipramine binding during recovery from depression Ellis PM, Beeston R, McJntosh CJ, Salmond CE, Cooke RR. Platelet ’H-imipramine binding during recovery from depression. Acta Psychiatr Scand 1992: 86: 108-112.
Decreased binding of tritiated imipramine to platelets has been considered to be a potential biological marker of depression. However, it has been unclear how binding values alter during treatment and recovery. This study investigated imipramine binding parameters and depressive symptoms in 25 patients suffering from major depression at entry to the study and 1, 3 and 6 months later. Although the initial B,, values were significantly lower in the depressed patients than in healthy subjects, it was not possible to establish a clear relationship between recovery from depression and B,,,. The power of this study to detect an effect of at least 10% of the variance in B,, due to factors related to recovery from depression was 0.78.
Although a considerable number of studies have reported a decrease in platelet imipramine binding in depressed patients (l), binding levels during and after recovery remain unclear. Most studies have reported that the maximal number of binding sites (Bmax) changes little during the first 1-3 weeks of treatment (2-4), except for those treated with clomipramine (5). Observations at later stages of treatment are not in agreement. Binding levels similar to those of control subjects have been found at 12-18 months in patients who had responded to electroconvulsive therapy (ECT) (6), 2 months after full remission (7) and after only 5 weeks of treatment with tricyclics (8). However, other workers have reported that there was no increase in B,, in patients at discharge from hospital after 20- 130 days of treatment (4), or after 6 weeks of treatment (9) or in recovered, drug-free patients at 1-2 years (10). Further investigation of this issue is therefore required.
Material and methods Twenty-five subjects suffering from a major depressive episode (DSM-I11 criteria (11)) and with a Hamilton Rating Scale for Depression (HRSD) score of more than 16 (17-item version) were recruited from admissions to a general hospital psychiatric unit (12). Forty healthy control subjects, free of mental disorder and scoring 4 or less on the 30item version of the General Health Questionnaire (13) were recruited from hospital staff and associ108
P. M. Ellis’, R. Beeston3,C. J. Mclntosh3, C. E. Salmond’, R. R. Cooke3
’
Departments of Psychological Medicine and Community Health, Wellington School of Medicine, University of Otago and Division of Laboratory Services, Wellington Hospital, New Zealand
Key words: imipramine binding; depression; platelet Dr. P.M. Ellis, MA BM FRANZCP, Senior Lecturer, Department of Psychological Medicine, Wellington School of Medicine, P.O. Box 7343, Wellington South, New Zealand Accepted for publication February 29, 1992
ates. All subjects were free of physical illness and were neither pregnant nor in the puerperium. None were suffering from an organic mental disorder or dependent on drugs or alcohol. Diagnoses were determined by a senior psychiatrist on the basis of a full psychiatric interview, ward observations and information from other key informants. A washout period of at least 5 days free of medication was seen as desirable, but was not adhered to when it was considered unethical to withhold treatment for this time. In this investigation a group of subjects who had been involved in a cross-sectional study were followed up over a 6-month period. The initial assessment of these subjects has been previously reported (14). Demographic data and details of medication taken in the preceding 6 months were recorded and patients were interviewed using the Composite International Diagnostic Interview (15). The severity of depression was assessed using the HRSD. Other measures used were a 6-point categorical scale completed by the clinician and a visual analogue scale completed by the patient, recording the severity at the time of assessment and also the maximal severity during that episode of illness. Imipramine binding was assayed as previously described (14). Blood samples were taken between 0730 and 1100. Platelet membranes were prepared from platelet-rich plasma by osmotic lysis and centrifugation (16) and imipramine binding was determined by a modification of the method of Briley
Imipramine binding after depression
et al. (17) using 'H-imipramine (Amersham, UK, specific activity 20 Ci/mM) at 8 different concentrations (1-8 nM). The final protein concentration in the assay tubes was near to 400 pg/ml. Nonspecific binding was estimated in the presence of 50 pM desipramine. B,,,, and K, were determined using an iterative, nonlinear curve-fitting technique (18). The intra-assay coefficient of variation in binding was 6.3 % and nonspecific binding represented 30 of total binding at all concentrations of 3H-imipramine used. Subjects then received routine treatment for depression at the discretion of their treating clinician. Depressed subjects were followed up 1, 3 and 6 months after entry into the study. On these occasions details of medication taken since the previous assessment were recorded, and symptoms over this period were documented using the depression section of the CIDI. Current symptom severity was assessed using HRSD, the categorical scale and the visual analogue scale. Patients were also asked to recall the maximal severity of their illness, Samples for imipramine binding were taken as before. The initial assessment data from these subjects formed part of a previous report (14). Complete binding data were available for all depressed subjects included in the present study. Subjects were classified as recovered during the follow-up period if they no longer satisfied criteria for DSM-I11 major depression and had a HRSD score of less than 8 (the conventional level for minimal or no depression). Other measures of recovery were global assessment rating scale values of 0 or 1 (indicating minimal or no depression) or visual analogue scale scores of less than 10% of maximal depression. returns to control It was hypothesized that B,, values only on full recovery. This may be better reflected by persistently low HRSD scores, and so the relationship between B,, and recovery at either or
0.3). The power of this study to detect an effect of at least 10% of the as due to factors related to recovvariance in B,, ery from depression was 0.78, and 0.99 for an effect accounting for at least 20"/, of the variance (19). The different measures of severity of depression were highly significantly inter-correlated (Visual Analogue Scale (VAS) vs Global Assessment Scale, Spearman's r = 0.78; Visual Analogue Scale vs HRSD = 0.78; HRSD vs global scale, Y = 0.88. P values all
Decreased binding of tritiated imipramine to platelets has been considered to be a potential biological marker of depression. However, it has been unclear how binding values alter during treatment and recovery. This study investigated imipramine binding parameters and depressive symptoms in 25 patients suffering from major depression at entry to the study and 1, 3 and 6 months later. Although the initial B,, values were significantly lower in the depressed patients than in healthy subjects, it was not possible to establish a clear relationship between recovery from depression and B,,,. The power of this study to detect an effect of at least 10% of the variance in B,, due to factors related to recovery from depression was 0.78.
Although a considerable number of studies have reported a decrease in platelet imipramine binding in depressed patients (l), binding levels during and after recovery remain unclear. Most studies have reported that the maximal number of binding sites (Bmax) changes little during the first 1-3 weeks of treatment (2-4), except for those treated with clomipramine (5). Observations at later stages of treatment are not in agreement. Binding levels similar to those of control subjects have been found at 12-18 months in patients who had responded to electroconvulsive therapy (ECT) (6), 2 months after full remission (7) and after only 5 weeks of treatment with tricyclics (8). However, other workers have reported that there was no increase in B,, in patients at discharge from hospital after 20- 130 days of treatment (4), or after 6 weeks of treatment (9) or in recovered, drug-free patients at 1-2 years (10). Further investigation of this issue is therefore required.
Material and methods Twenty-five subjects suffering from a major depressive episode (DSM-I11 criteria (11)) and with a Hamilton Rating Scale for Depression (HRSD) score of more than 16 (17-item version) were recruited from admissions to a general hospital psychiatric unit (12). Forty healthy control subjects, free of mental disorder and scoring 4 or less on the 30item version of the General Health Questionnaire (13) were recruited from hospital staff and associ108
P. M. Ellis’, R. Beeston3,C. J. Mclntosh3, C. E. Salmond’, R. R. Cooke3
’
Departments of Psychological Medicine and Community Health, Wellington School of Medicine, University of Otago and Division of Laboratory Services, Wellington Hospital, New Zealand
Key words: imipramine binding; depression; platelet Dr. P.M. Ellis, MA BM FRANZCP, Senior Lecturer, Department of Psychological Medicine, Wellington School of Medicine, P.O. Box 7343, Wellington South, New Zealand Accepted for publication February 29, 1992
ates. All subjects were free of physical illness and were neither pregnant nor in the puerperium. None were suffering from an organic mental disorder or dependent on drugs or alcohol. Diagnoses were determined by a senior psychiatrist on the basis of a full psychiatric interview, ward observations and information from other key informants. A washout period of at least 5 days free of medication was seen as desirable, but was not adhered to when it was considered unethical to withhold treatment for this time. In this investigation a group of subjects who had been involved in a cross-sectional study were followed up over a 6-month period. The initial assessment of these subjects has been previously reported (14). Demographic data and details of medication taken in the preceding 6 months were recorded and patients were interviewed using the Composite International Diagnostic Interview (15). The severity of depression was assessed using the HRSD. Other measures used were a 6-point categorical scale completed by the clinician and a visual analogue scale completed by the patient, recording the severity at the time of assessment and also the maximal severity during that episode of illness. Imipramine binding was assayed as previously described (14). Blood samples were taken between 0730 and 1100. Platelet membranes were prepared from platelet-rich plasma by osmotic lysis and centrifugation (16) and imipramine binding was determined by a modification of the method of Briley
Imipramine binding after depression
et al. (17) using 'H-imipramine (Amersham, UK, specific activity 20 Ci/mM) at 8 different concentrations (1-8 nM). The final protein concentration in the assay tubes was near to 400 pg/ml. Nonspecific binding was estimated in the presence of 50 pM desipramine. B,,,, and K, were determined using an iterative, nonlinear curve-fitting technique (18). The intra-assay coefficient of variation in binding was 6.3 % and nonspecific binding represented 30 of total binding at all concentrations of 3H-imipramine used. Subjects then received routine treatment for depression at the discretion of their treating clinician. Depressed subjects were followed up 1, 3 and 6 months after entry into the study. On these occasions details of medication taken since the previous assessment were recorded, and symptoms over this period were documented using the depression section of the CIDI. Current symptom severity was assessed using HRSD, the categorical scale and the visual analogue scale. Patients were also asked to recall the maximal severity of their illness, Samples for imipramine binding were taken as before. The initial assessment data from these subjects formed part of a previous report (14). Complete binding data were available for all depressed subjects included in the present study. Subjects were classified as recovered during the follow-up period if they no longer satisfied criteria for DSM-I11 major depression and had a HRSD score of less than 8 (the conventional level for minimal or no depression). Other measures of recovery were global assessment rating scale values of 0 or 1 (indicating minimal or no depression) or visual analogue scale scores of less than 10% of maximal depression. returns to control It was hypothesized that B,, values only on full recovery. This may be better reflected by persistently low HRSD scores, and so the relationship between B,, and recovery at either or
0.3). The power of this study to detect an effect of at least 10% of the as due to factors related to recovvariance in B,, ery from depression was 0.78, and 0.99 for an effect accounting for at least 20"/, of the variance (19). The different measures of severity of depression were highly significantly inter-correlated (Visual Analogue Scale (VAS) vs Global Assessment Scale, Spearman's r = 0.78; Visual Analogue Scale vs HRSD = 0.78; HRSD vs global scale, Y = 0.88. P values all
