[Monitoring antidepressant use in acute hospital]

[Article in Spanish]

Redondo Capafons S, Garriga Biosca MR, Pla Poblador R.

Servicio de Farmacia. Hospital Mutua de Terrassa. Barcelona. Spain. farmacia mutuaterrassa.es

OBJECTIVE: To carry out a prospective study on the current use of antidepressants (ADs) in an acute hospital, in order to determine the prescription sources, therapeutic indications, safety and monitoring of these drugs and their use at patient discharge. METHOD AND RESULTS: To this end the therapeutic drug profiles of non-psychiatric inpatients treated with tri-cyclic antidepressants, selective serotonin re-uptake inhibitors (SSRIs) or monoamine oxidase inhibitors (MAOIs) were prospectively reviewed. The following was collected from the patientsa medical record: reason for admittance, AD indication, prescription source (primary care or in-hospital), modifications of antidepressant treatment during stay, drug-related adverse events (DRAEs), interactions with other drugs, and whether patients were still on antidepressants upon discharge. The mean numer of daily inpatients was 382.6, of which 4.4% received ADs (11-25). Females were 67.5% and males were 32.5%, with a mean age of 67 years (37-92). The total number of patients studied was 126. Prescribed SSRIs represented 73% of cases (92), whereas tricyclic antidepressants represented 27% (34). Prescription originated in primary care for 79.4% of cases (29% tricyclics, 71% SSRIs) and within hospital for 20.6% of cases (tricyclics 11, SSRIs 15), p = 0.02. AD indications were endogenous depression in 72.2%, reactive depression in 7.1%, neuropathic pain in 7.1%, cancer-related pain in 2.4%, and indications not specified in medical records in 11.1%. Treatment was ongoing at patient discharge in 97.5% of cases. CONCLUSIONS: AD prescription source was most commonly primary care. Prescription of ADs for unauthorised indications was seen: management of dementia in the elderly and shyness, support treatment for fibromyalgia, and migraine prophylaxis. In virtually all inpatients on ADs prescriptions were maintained without modification during stay. In the follow-up of patients on ADs, no clinically significant interactions leading to treatment changes were seen.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=12717565&dopt=Abstract antidepressant




Prevalence of antidepressant use among older people: population-based observations.

Mamdani M, Herrmann N, Austin P.

Institute for Clinical Evaluative Sciences, Sunnybrook and Women's College Health Sciences Centre, Toronto, Ontario, Canada.

OBJECTIVE: To assess the prevalence of antidepressant use with respect to age, gender, and time during a 5-year period from 1993 to 1997. DESIGN: A retrospective, population-based study in which data regarding a cross-sectional series of annual antidepressant use were obtained from administrative claims and census databases for more than 1.4 million older persons during calendar years 1993 through 1997. PARTICIPANTS: All residents of Ontario aged 65 or older. MAIN OUTCOME MEASURES: Changes in the prevalence of antidepressant users as a function of age group, gender, and time. RESULTS: A general, positive, linear trend in the prevalence of antidepressant users with increasing age group was consistently detected regardless of gender and year assessed (P < .001 for both genders and all years). The age-adjusted relative risk of women being dispensed an antidepressant relative to men was significantly higher during each year but seemed to decrease slightly over time: 1.74 (95% CI, 1.72-1.76) in 1993 and 1.65 (95% CI, 1.63-1.67) in 1997. The multiple linear regression model revealed significant relationships between the prevalence of antidepressant users and increasing age group, female gender, and increasing year of assessment (P < .001 for each variable). The prevalence was observed to range from a low of 5.6% in 65 to 69-year-old men in 1993 to a high of 17.2% among 85 to 89-year-old women in 1997. CONCLUSIONS: Our findings reveal that the prevalence of antidepressant users is dynamic and is significantly and independently associated with age, gender, and time of assessment.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=10573446&dopt=Abstract antidepressant




Use of antidepressants by general practitioners and psychiatrists in Australia.

McManus P, Mant A, Mitchell P, Britt H, Dudley J.

Department of Health and Ageing, Canberra, Australian Capital Territory 2605, Australia. peter.mcmanus health.gov.au

OBJECTIVE: To examine the antidepressant prescribing patterns of psychiatrists and general practitioners (GPs) in Australia, focusing specifically on: the prescribed daily dose, the relative proportions (from subsidized dispensing data) of prescriptions written, and how these proportions change over time for a newly listed antidepressant drug (using paroxetine as an example). METHOD: Retrospective analyses of subsidized claims data (comprising nearly 90% of the community supply of antidepressants) and prescriber surveys. RESULTS: General practitioners prescribe 86% of subsidized antidepressants in Australia. Almost three-quarters of the antidepressant prescriptions prescribed in primary care management are also initiated by a GP. Psychiatrists prescribed higher doses than general practitioners for all the antidepressants examined. For paroxetine, a higher than average proportion of scripts were written by psychiatrists when the drug was initially available and it only reached the GP/psychiatrist split seen with an established drug in the same therapeutic class (fluoxetine) four years after marketing. The most prominent type of depression that GPs believed they were treating was 'chronic mild depression', which contrasts with the subsidized indication for all newer antidepressant classes of 'major depressive disorders'. CONCLUSIONS: General practitioners are the major providers of treatment for depression in Australia. When writing prescriptions for tricyclic antidepressants GPs use doses lower than those recommended for major depression, however, most management in primary care is not for conditions regarded by the GP as major depression. A significant number of prescriptions for the newer antidepressants may not accord with the Pharmaceutical Benefits Scheme (PBS) restrictions for use.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=12656957&dopt=Abstract antidepressant




Add-on polytherapy with antidepressants and its significance in inpatients with major depression.

Wada K, Yamada N, Hamamura T, Suzuki H, Nakano Y, Kuroda S.

Department of Neuropsychiatry, Okayama University Medical School, Japan. kwada12 cc.okayama-u.ac.jp

Add-on polytherapy with antidepressant agents was reviewed in 42 inpatients with major depression diagnosed according to the ICD-10 criteria. Twenty-eight (67.7%) patients were treated with two or more antidepressants. The most frequent combination consisted of a tricyclic antidepressant and a non-tricyclic antidepressant. Nineteen (67.8%) patients of the polytherapy group were treated with a dosage equivalent to 150 mg/day of tricyclic antidepressant. Clinically, not every patient with major depression can tolerate the adverse side effects induced by an effective dose of a single tricyclic antidepressant. From this viewpoint, add-on polytherapy with antidepressants could be one of the treatment options, especially for such intolerant patients.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=10595679&dopt=Abstract antidepressant




Depression treatment in a sample of 1,801 depressed older adults in primary care.

Unutzer J, Katon W, Callahan CM, Williams JW Jr, Hunkeler E, Harpole L, Hoffing M, Della Penna RD, Noel PH, Lin EH, Tang L, Oishi S.

Center for Health Services Research, UCLA Neuropsychiatric Institute, Los Angeles, California 90024, USA. unutzer ucla.edu

OBJECTIVES: To examine rates and predictors of lifetime and recent depression treatment in a sample of 1,801 depressed older primary care patients DESIGN: Cross sectional survey data collected from 1999 to 2001 as part of a treatment effectiveness trial. SETTING: Eighteen primary care clinics belonging to eight organizations in five states. PARTICIPANTS: One thousand eight hundred one clinic users aged 60 and older who met diagnostic criteria for major depression or dysthymia. MEASUREMENTS: Lifetime depression treatment was defined as ever having received a prescription medication, counseling, or psychotherapy for depression. Potentially effective recent depression treatment was defined as 2 or more months of antidepressant medications or four or more sessions of counseling or psychotherapy for depression in the past 3 months. RESULTS: The mean age +/- standard deviation was 71.2 +/- 7.5; 65% of subjects were women. Twenty-three percent of the sample came from ethnic minority groups (12% were African American, 8% were Latino, and 3% belonged to other ethnic minorities). The median household income was $23,000. Most study participants (83%) reported depressive symptoms for 2 or more years, and most (71%) reported two or more prior depressive episodes. About 65% reported any lifetime depression treatment, and 46% reported some depression treatment in the past 3 months, although only 29% reported potentially effective recent depression treatment. Most of the treatment provided consisted of antidepressant medications, with newer antidepressants such as selective serotonin reuptake inhibitors constituting the majority (78%) of antidepressants used. Most participants indicated a preference for counseling or psychotherapy over antidepressant medications, but only 8% had received such treatment in the past 3 months, and only 1% reported four or more sessions of counseling. Men, African Americans, Latinos, those without two or more prior episodes of depression, and those who preferred counseling to antidepressant medications reported significantly lower rates of depression care. CONCLUSION: The findings suggest that there is considerable opportunity to improve care for older adults with depression. Particular efforts should be focused on improving access to depression care for older men, African Americans, Latinos, and patients who prefer treatments other than antidepressants.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=12657070&dopt=Abstract antidepressant




Are the newer antidepressant drugs as effective as established physical treatments? Results from an Australasian clinical panel review.

Parker G, Mitchell P, Wilhelm K, Menkes D, Snowdon J, Schweitzer I, Grounds D, Skerritt P, Roy K, Hadzi-Pavlovic D.

School of Psychiatry, University of New South Wales, Randwick, Australia. g.parker unsw.edu.au

OBJECTIVE: The aim of this study was to determine, in a clinical panel sample, the extent to which patients with depression (and melancholic and non-melancholic subtypes) judged the effectiveness of previously received antidepressant treatments, particularly the comparative effectiveness of the older and newer antidepressant drugs. METHOD: Twenty-seven Australasian psychiatrists assessed 341 non-psychotic depressed patients and rated the extent to which previous antidepressant treatments had been effective. Patients were assigned to 'melancholic' and residual 'non-melancholic' categories by two processes (DSM-IV decision rules, and a cluster analysis-derived allocation) and treatment effectiveness examined within each category. RESULTS: Electroconvulsive therapy (both bilateral and unilateral) was judged as highly effective by both melancholic and non-melancholic patients. Antipsychotic medication similarly rated highly (but was judged as more effective by the non-melancholic than melancholic patients). The tricyclics and irreversible monoamine oxidase inhibitors (MAOIs) were rated as more effective by the whole sample than several newer antidepressant classes (including the selective serotonin re-uptake inhibitors [SSRIs], venlafaxine, mianserin and moclobemide), whether effectiveness was examined dimensionally or categorically. Comparison of the overall tricyclic and SSRI classes indicated that any superior tricyclic effectiveness was specific to the melancholic subjects. CONCLUSIONS: Despite methodological limitations intrinsic to such clinical panel data, the judged greater effectiveness of the older antidepressants (tricyclics and irreversible MAOIs) for melancholic depression is of importance. If valid, such data are of intrinsic clinical relevance but also have the potential to inform us about the neurobiological determinants of 'melancholia' and pharmacological actions which contribute to its effective treatment.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=10619215&dopt=Abstract antidepressant




Lysosomal trapping as an important mechanism involved in the cellular distribution of perazine and in pharmacokinetic interaction with antidepressants.

Daniel WA, Wojcikowski J.

Polish Academy of Sciences, Institute of Pharmacology, Department of Pharmacokinetics and Drug Metabolism, Krakow.

Perazine, a piperazine-type phenothiazine neuroleptic, is the most frequently chosen drug for combination with antidepressants in the therapy of complex or 'treatment-resistant' psychiatric illnesses. The aim of the present study was to investigate the contribution of lysosomal trapping to the total tissue uptake of perazine, and the pharmacokinetic interaction between the neuroleptic and antidepressants. Experiments were carried out on slices of different rat organs regarded as a system with functional lysosomes. To distinguish between lysosomal trapping and tissue binding, the experiments were performed in the absence or presence of 'lysosomal inhibitors', i.e. the lysosomotropic compound ammonium chloride or [H+] ionophore monensin, which abolish the pH-gradient of lysosomes. Under steady-state conditions, the highest tissue uptake of perazine was observed for the adipose tissue, which descended in the following order: the adipose tissue>lungs>liver>heart=brain>kidneys>muscles. The contribution of lysosomal trapping to the total tissue uptake amounted to about 40% in the liver, brain and muscles, to 30% in the kidneys, and to 25% in the heart and lungs. In the adipose tissue, no lysosomotropism of perazine was observed. Of the psychotropics studied, perazine was the only drug showing such a high degree of lysosomal trapping in muscles and distinct lysosomotropic properties in the heart. Perazine and the antidepressants used, both tricyclic (imipramine, amitriptyline) and selective serotonin reuptake inhibitors (fluoxetine, sertraline), mutually decreased their tissue uptake. The potency of imipramine to decrease perazine uptake was similar to that of the 'lysosomal inhibitors'. Other antidepressants seemed to exert a somewhat weaker effect. The above interactions between perazine and antidepressants were not observed in the presence of ammonium chloride, which indicates that they proceeded at the level of lysosomal trapping. The adipose tissue in which the drug uptake was not affected by the 'lysosomal inhibitors' was not the site of such an interaction. Ammonium chloride did not affect the drug metabolism in liver slices; other tissues displayed only a negligible biotransformation of the psychotropics studied. A parallel metabolic interaction between perazine and tricyclic antidepressants took part in liver slices (i.e. perazine and antidepressants mutually inhibited their metabolic pathways), but the influence of such an interaction on the lysosomal uptake of the parent compounds in liver slices did not seem to be great. A substantial decrease in concentrations of the drugs in lysosomes (depot form) observed in vitro may lead to an increase in the concentration in vivo of the neuroleptic and antidepressants at the site of action, which, in turn, may increase the risk of cardiotoxic and anticholinergic side-effects of tricyclic antidepressants and sedative and extrapyramidal effects of the neuroleptic.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=10625116&dopt=Abstract antidepressant




Among fatal poisonings dextropropoxyphene predominates in younger people, antidepressants in the middle aged and sedatives in the elderly.

Jonasson B, Jonasson U, Saldeen T.

Department of Forensic Medicine, University of Uppsala, Sweden.

To compare the characteristics of dextropropoxyphene (DXP) poisoning victims with those of victims of poisonings by antidepressants and sedatives, we examined all fatal poisonings due to DXP, antidepressants or sedatives among autopsies performed at one department of forensic medicine in Sweden during the six-year period from 1992 to 1997. In 202 cases, death was classified as fatal poisonings by DXP, antidepressants or sedatives. DXP caused death in 78 cases (39%), antidepressants in 49 (24%), and sedatives in 75 (37%). DXP as a single preparation was predominant in causing death. The second compound, flunitrazepam, caused death in 30 cases (15%). The victims of poisonings by DXP, antidepressants, or sedatives shared a similar history of alcohol/drug abuse, depression and somatic illness. They were mostly living alone at the time of death (>60%), the majority died at home (81%), and suicide was the most frequent manner of death (73%). Age seemed to be an important characteristic regarding the choice of drug. Younger people predominantly died of DXP (mean age 43 years, 95% confidence interval, CI 39-47), and elderly people of sedatives (mean age 59 years, CI 55-63). Antidepressants were found mainly in middle-aged victims (mean age 51 years, CI 48-54). The predominance of sedatives among the elderly might be explained by a very high prescription rate of such drugs in older age groups, but prescription rate could not explain the DXP predominance among younger people. We hypothesize that younger people are more prone to abuse therapeutic drugs for euphoric reasons than elderly people, and that because of its high toxicity, DXP leads to accidental deaths more often than sedatives.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=10641912&dopt=Abstract antidepressant