Concomitant Psychotropic Drugs Research Articles

Evaluating the Impact of an Educational Program on Practice Patterns of Canadian Family Physicians Interested in Depression Treatment.

BACKGROUND: Depression is frequently unrecognized and undertreated. Therefore, there is a need to increase the knowledge and skills of primary care physicians regarding the diagnosis and treatment of depression. The aim of this study was to provide, and evaluate the impact of, a brief educational program with a number of practice tools and resources in order to improve family physicians' knowledge, diagnosis, and treatment of depression. METHODS: Two educational programs (general and enhanced) were delivered to family physicians interested in depression treatment. The enhanced program focused on more practical clinical issues such as use of diagnostic and symptom assessment tools, recommended dosing of citalopram, how to initiate and discontinue treatment, and relapse prevention. Physicians' knowledge of depression was assessed pretraining and posttraining. Chart audits were conducted for 6 months. Primary endpoints were recognition of depression and pharmacologic management (initial dose, maximum dose, length of treatment, adverse events, and concomitant psychotropic drugs). Secondary endpoints were patient satisfaction with treatment, compliance, withdrawal from the study, treatment outcome, use of adjunctive psychotherapy, and number of office visits. RESULTS: There was a global increase in physicians' knowledge of depression in the short term. Physicians in the enhanced group were more likely to use a symptom-based diagnostic checklist, record the diagnosis of depression, and prescribe the recommended initial dose of citalopram, and they referred less frequently for adjunctive psychotherapy. No difference between educational intervention groups was found in patient satisfaction, compliance, and treatment outcome. CONCLUSIONS: A well-designed brief, simple, and low-cost educational program can increase family physicians' knowledge of depression, improve their diagnostic skills, and optimize their treatment of depression.

The use of concomitant medications in psychiatric inpatients treated with either olanzapine or other antipsychotic agents: A naturalistic study at a state psychiatric hospital

Concomitant medications are frequently used in the treatment of resistant psychiatric conditions to augment the primary psychotropic agent or to ameliorate side effects. The present study evaluated the prescription of concomitant psychiatric medications for psychiatric inpatients that were prescribed either olanzapine at its first commercial availability or another first-line antipsychotic agent. Sixty-nine newly admitted patients (mainly with schizophrenia) who were prescribed either olanzapine ( n=35) or another first-line antipsychotic agent ( n=34) were assessed (for the prescription of other concomitant psychotropic drugs) before (2–4 weeks prior to study) and following 8 weeks of treatment (unless discharged sooner). The results indicate that significantly fewer olanzapine-treated subjects were prescribed anticholinergic agents as compared to those prescribed other first-line antipsychotic agents, and a similar trend was noted in the prescription of mood stabilizers as well. Olanzapine-treated subjects used less as needed (PRN) antipsychotic medication compared to pre-olanzapine treatment period. Olanzapine-treated subjects used more anxiolytic agents compared to the control group in the early stages of treatment, probably due to the greater baseline severity of illness. These data suggest that olanzapine use is associated with less use of anticholinergic and mood-stabilizing agents as compared to older antipsychotic agents. These results also suggest that there is less need for PRN antipsychotic medication following olanzapine treatment. More severely ill subjects may require more anxiolytics during olanzapine initiation. The need for less anticholinergic and mood-stabilizing agent use with olanzapine could lead to greater adherence to long-term treatment and perhaps decreased cost (i.e. use of blood and organ system monitoring with mood stabilizers). At the end of treatment, olanzapine-treated subjects had statistically significantly lesser concomitant medicine usage compared to control subjects.

The effect of repeated bilateral electroconvulsive therapy on seizure threshold.

Seizure threshold was measured by empirical titration in 28 patients referred for bilateral electroconvulsive therapy to treat depressive illness at the outset of treatment and after another six treatments. No patient was given antiepileptic drug treatment, and anesthetic technique and concomitant psychotropic drug treatment were fixed. The average (+/- SD) initial seizure threshold measured by set charge was 79.5 mC (+/- 33.4 mC), and this increased to 95.5 mC (+/- 37.9 mC). The average percentage increase was 22.8% (95% confidence interval, 13.7% to 31.8%). The seizure threshold measured by set charge did not change in 15 patients (54%), and there was no significant relation between change in seizure threshold and patient sex, change in seizure duration measured by cuff technique, or global clinical improvement during the course of treatment.

The Effect of Age and Concomitant Treatment with Other Psychoactive Drugs on Serum Concentrations of Citalopram Measured with a Nonenantioselective Method

We measured citalopram and desmethylcitalopram concentrations in serum from 169 psychiatric patients, who were treated with common therapeutic drug doses. Altogether 202 serum samples were assayed by a nonenantioselective high-performance liquid chromatography (HPLC) method. The results indicate that the kinetic variability (maximum concentration/minimum concentration) in dose- and weight-related serum citalopram (10.6-fold) and desmethylcitalopram (7.2-fold) is large even during monotherapy. Log serum citalopram (r = 0.36, p < 0.05) and desmethylcitalopram (r = 0.51, p < 0.01) concentrations of individual patients increased significantly with increasing drug doses. Dose- and weight-related (calculated as mg/kg dose basis) log serum citalopram (r = 0.29) but not desmethylcitalopram (r = 0.06) concentrations increased with aging (p < 0.001). No sex-related differences were found. Nineteen patients (19 samples) had concomitant treatment with neuroleptics, 84 patients (101 samples) with benzodiazepines, and 18 patients (28 samples) with tricyclic antidepressants. The concentrations in these patients were compared with those of 48 nonsmoking patients (54 samples) without any concomitant psychotropic drug treatment. None of the single neuroleptics alone had a significant effect on dose- and weight-related serum citalopram or desmethylcitalopram concentrations. However, citalopram concentrations increased by 121% (338 +/- 165 vs. 747 +/- 505, mean +/- SD; p < 0.01) and desmethylcitalopram by 85% (124 +/- 53 vs. 229 +/- 138; p < 0.05) when neuroleptics were pooled. Among single benzodiazepines, only alprazolam increased serum citalopram (338 +/- 165 vs. 391 +/- 267; p < 0.01) and desmethylcitalopram (124 +/- 53 vs. 186 +/- 175; p < 0.01) concentrations. When all the benzodiazepines were pooled, they still increased the serum concentration of the parent drug by 23% (338 +/- 165 vs. 414 +/- 303; p < 0.05) and those of the metabolite by 47% (124 +/- 53 vs. 182 +/- 163; p < 0.01). In patients who were simultaneously treated with clomipramine, serum citalopram (338 +/- 165 vs. 655 +/- 409; p < 0.001) and desmethylcitalopram (124 +/- 53 vs. 435 +/- 347; p < 0.001) concentrations were consistently higher than those of the controls. Even when the tricyclic antidepressants were pooled, they increased citalopram concentrations by 44% (338 +/- 165 vs. 486 +/- 312; p < 0.001) and desmethylcitalopram concentrations by 111% (124 +/- 53 vs. 261 +/- 260; p < 0.001). The results suggest that interindividual variability in serum citalopram concentrations is pronounced and that increased serum citalopram levels are related to advancing age and concomitant treatment with other psychotropic drugs. The citalopram dose should therefore ideally be individualized by therapeutic drug monitoring.

Serum mianserin and ageing

1. 1. Mianserin is a tetracyclic antidepressant with relatively few anticholinergic and cardiovascular sideeffects. Its clinical efficacy is comparable to that of tricyclic antidepressants. It is widely used in Europe, especially in elderly outpatients. 2. 2. In the present studies, the authors have evaluated the efficacy of mianserin as well as the effects of ageing and concomitant psychotropic drugs on serum mianserin concentrations in 169 depressive psychiatric inpatients. 3. 3. In the patients the mean serum mianserin concentrations or their interindividual variations did not differ between the old, middle-aged, and young age groups. Furthermore, elderly women and men did not differ from each other for their dose-related drug concentrations. Neither were any differences found in serum mianserin concentrations between the older (≥75 years) and younger elderly (65–74). As is the case with TCAs, the co-administration of neuroleptics increased serum mianserin concentrations in the elderly. When comparing the therapeutic response and serum mianserin concentrations the authors found that the patients with good clinical improvement had higher mean serum mianserin concentrations than those without efficacy. 4. 4. There seem to be no clinically important changes in the phannacokinetics of mianserin with advancing age. The present results do not support the claim that the therapeutic profile of this drug is altered with advancing age. Mianserin can be regarded as an antidepressant with relatively few side-effects in the elderly.

The effect of lithium on thyroid functioning: A controlled study

THE EFFECTS of lithium on thyroid function have recently been reviewed by SHOPSIN.~ Anecdotal reports of hypothyroidism and goiter are described. Controlled human studies have been done by SEDVALL et aL2 and COOPER and SIMPSON.~ SEDVALL et al.2 gave lithium to 14 manic-depressives and used 11 patients receiving phenothiazines, with other diagnoses as controls. The lithium treatment was begun, “about one week after admission to the hospital. . . . Tests of thyroid function were performed during the first week after admission to hospital and 10 to 14 days later. At the latter time lithium treatment in the manic-depressive patients had been maintained for 7 to 20 days.” A personal communication from the senior author indicates that the initial thyroid function tests were all done prior to initiation of lithium, and the second series of tests were done 7 -20 days after lithium was begun, and not 10-14 days as published. Compared to the first test, there was a significant decrease in protein bound iodine (PBI) and a significant increase in the percentage of orally administered radioactive iodine (24 hr RAIl”l) in the thyroid after 24 hr, in the lithium treated manic-depressed patients. There were no changes in the control patients. It is difficult to evaluate the significance of these results because the control group had different diagnoses and received an active drug that may affect thyroid function tests.4 COOPER and SIMPSON~ compared PBI and free thyroxine in 25 manic-depressives two weeks after initiating lithium treatment to 139 other psychiatric admissions (excluding organic psychoses) who had blood drawn while drug free. The PBI and free thyroxine were significantly reduced in the lithium group. They also compared RAIU (24 hr) before, and 12-16 weeks after lithium treatment in 12 manic-depressives and found a significant increase following lithium treatment. BURROW et aL5 studied 9 patients before and after 3-4 weeks of lithium therapy. Some patients received concomitant psychotropic drugs and perhaps diphenylhydantoin or oral contraceptives. The patients were hospitalized and diagnosed as having “mood disorders” although one patient may have been hospitalized for a seizure disorder. They found that *We wish to acknowledge the help we received in the statistical computations from Mrs. Dolores Millan