Adverse Drug Reactions: A Retrospective Review of Hospitalized Patients at a State Psychiatric Hospital

Background: There is a paucity of information regarding adverse drug reactions (ADRs) in psychiatric patients. Information on common and preventable ADRs (pADRs) in psychiatric patients will allow for targeted improvement projects.Objective: To characterize reported ADRs and pharmacist interventions to prevent ADRs in an extended-care state psychiatric hospital.Methods: Four years of ADR reports were assessed for probability, reaction severity, pharmacological class of medication involved, preventability, change in therapy, and transfers to a medical facility. The pharmacist intervention database was queried for interventions classified as “prevention of ADR.” The interventions were assessed for type of medication and recommendation acceptance.Results: Medication classes responsible for ADRs included mood stabilizers (30%), typical antipsychotics (25%), atypical antipsychotics (25%), and antidepressants (8%). Nine percent resulted in transfer to a medical facility. Of all ADRs, 34.4% were pADRs; mood stabilizers (41%) and atypical antipsychotics (27%) were the most common pADRs. The most common causes of pADRs were supratherapeutic serum concentrations, drug-drug interactions, and history of reaction. There were 87 pharmacist interventions that were classified as “prevention of ADR,” and the acceptance rate of pharmacists’ recommendations was 96.5%. Mood stabilizers (20%), atypical antipsychotics (17%), and typical antipsychotics (11%) were commonly associated with prevented ADRs. Lithium accounted for 13.8% of prevented ADRs; these ADRs were most often due to a drug–drug interaction with a nonsteroidal anti-inflammatory drug.Conclusions: ADRs were most commonly associated with mood stabilizers and antipsychotics, and pADRs were common. There is an opportunity to provide education to medical staff on therapeutic drug monitoring and drug–drug interactions for these classes, particularly lithium.     

Selective serotonin reuptake inhibitor augmentation in the treatment of negative symptoms of schizophrenia

The treatment of negative symptoms of schizophrenia presents a major clinical challenge. This review examines the evidence pertaining to the efficacy, tolerability and safety of adding selective serotonin reuptake inhibitors (SSRIs) to antipsychotic agents in the treatment of negative symptoms in schizophrenia. Important methodological issues such as differentiating primary and secondary negative symptoms are discussed. The balance of available evidence indicates that at least some SSRIs, fluvoxamine and fluoxetine, can ameliorate primary negative symptoms in chronic schizophrenia patients who are treated with typical antipsychotics. The combination is safe and well tolerated although, as antipsychotic drug concentrations may be elevated, attention to dose and drug monitoring should be considered as appropriate. The effect of SSRI augmentation of atypical antipsychotics requires further study. Combination with clozapine may require particular caution because of potential toxicity if serum clozapine levels rise steeply. SSRI augmentation may be a useful addition to the treatment of schizophrenia.     

老年精神障碍患者精神药物临床使用分析

目的:了解老年精神障碍患者精神药物临床使用情况。方法:收集肇庆市第三人民医院2008年1月1日-2008年12月31日出院,年龄60a或以上老年住院精神障碍患者的病历175份,采用限定日剂量(DDD)和药物利用指数(DUI)对精神药物的使用进行回顾性分析。结果:非典型抗精神病药利培酮的使用频率居首位,其次为奋乃静;抗抑郁药中舍曲林居首位,其次为帕罗西汀;在联合用药方面,抗精神病药与苯二氮艹卓类药物、抗抑郁药与苯二氮卓艹类药物和情感稳定剂、抗精神病药与抗抑郁药联用较多。在使用的33种精神药物中除舒必利、丙戊酸钠、阿普唑仑、三唑仑外,其余药物的DUI均≤1.0。结论:我院对老年精神障碍患者精神药物的使用基本合理。非典型抗精神病药、新型抗抑郁药的使用越来越多。     

A nationwide prospective study on prescribing pattern of antidepressant drugs in Italian primary care

Purpose

Our purpose was to explore antidepressant drug (AD) prescribing patterns in Italian primary care.

Methods

Overall, 276 Italian general practitioners (GPs) participated in this prospective study, recruiting patients >18 years who started AD therapy during the enrolment period (January 2007 to June 2008). During visits at baseline and 3, 6, and 12 months, data about patients’ characteristics and AD treatments were collected by the GPs. Discontinuation rate among new users of AD classes [i.e., selective serotonin reuptake inhibitors (SSRI); tricyclics (TCAs); other ADs) were compared. Logistic regression analyses were performed to identify predictors of AD discontinuation.

Results

SSRIs were the most frequently prescribed ADs (N?=?1,037; 75.3 %), especially paroxetine and escitalopram. SSRIs were more likely to be prescribed because of depressive disorders (80 %), and by GPs (51.1 %) rather than psychiatrists (31.8 %). Overall, 27.5 % (N?=?378) of AD users discontinued therapy during the first year, mostly in the first 3 months (N?=?242; 17.6 %), whereas 185 (13.4 %) were lost to follow-up. SSRI users showed the highest discontinuation rate (29 %). In patients with depressive disorders, younger age, psychiatrist-based diagnosis, and treatment started by GPs were independent predictors of SSRI discontinuation.

Conclusions

In Italy, ADs—especially SSRIs—are widely prescribed by GPs because of depressive/anxiety disorders. Active monitoring of AD users in general practice might reduce the AD discontinuation rate.     

Adverse drug reaction monitoring in psychiatry out-patient department of an Indian teaching hospital

Objectives:

Adverse drug reactions (ADRs) to psychotropic agents are common and can lead to noncompliance or even discontinuation of therapy. There is paucity of such data in the Indian context. We deemed it worthwhile to assess the suspected ADR profile of psychotropic drugs in an ambulatory setting in a public teaching hospital in Kolkata.

Materials and Methods:

A longitudinal observational study was conducted in the outpatient department (OPD) of the concerned psychiatry unit. Twenty consecutive patients per day, irrespective of their psychiatric diagnosis, were screened for suspected ADRs, 2 days in a week, over 15 months. Adverse event history, medication history and other relevant details were captured in a format as adopted in the Indian National Pharmacovigilance Programme. Causality was assessed by criteria of World Health Organization-Uppsala Monitoring Center (WHO-UPC).

Results:

We screened 2000 patients (68.69% males, median age 34.4 years), of whom 429 were suspected of having at least one ADR; 84 cases had insufficient evidence about causality (WHO-UMC causality status “unlikely”) and were excluded from further analysis. Thus, 17.25% (95% confidence interval: 15.59-18.91%) of our study population reported ADRs with at least “possible” causality. Of 352 events recorded, 327 (92.90%) were “probable” and the rest “possible”. None was labeled “certain” as rechallenge was not performed. Patients received a median of 3.2 psychotropic drugs each. Thirty-three different kinds of ADRs were noted, including tremor (19.60%), weight gain (15.34%) and constipation (14.49%). Among the incriminated drugs, antipsychotics represented the majority (57.10%), with olanzapine topping the list.

Conclusions:

This study offers a representative profile of ADRs to be expected in psychiatry out-patients in an Indian public hospital. Establishment of a psychotropic drug ADR database can be a worthy long-term goal in the Indian context.     

Clozapine discrimination with a low training dose distinguishes atypical from typical antipsychotic drugs in rats

Rationale: Previous drug discrimination studies with clozapine have not reliably distinguished between atypical and typical antipsychotics. Objectives: The present study was conducted to determine whether low-dose clozapine drug discrimination could distinguish atypical from typical antipsychotics. Methods: Rats were trained to discriminate 1.25 mg/kg clozapine from vehicle in a two-lever drug discrimination procedure. Results: Generalization testing revealed full substitution with the atypical antipsychotics olanzapine (90.3% maximum generalization), sertindole (99.8%), and risperidone (87.1%) and partial substitution for quetiapine (seroquel, 66.4%) and the typical antipsychotics haloperidol (56.8%) and thioridazine (74.3%). Remoxipride (23.1%) and the typical antipsychotics chlorpromazine (27.9%) and fluphenazine (29.5%) did not reliably substitute for clozapine. Conclusions: In contrast to previous clozapine drug discrimination studies with higher training doses, the atypical antipsychotics olanzapine, sertindole, and risperidone reliably substituted for clozapine while typical antipsychotics did not. These results suggest that low-dose clozapine drug discrimination may be a more sensitive assay for distinguishing atypical from typical antipsychotic drugs. Received: 3 August 1999 / Final version: 9 December 1999     

对某住院患者使用抗精神病药物致不良反应报告的分析

目的：分析某院住院患者使用抗精神病药致药物不良反应（adverse drug reaction,ADR）的特点,旨在提高患者用药的安全性。方法：回顾性分析该院2013-2018年上报的374例抗精神病药物致ADR的报告,依据患者基本信息、用药情况、药品品种、ADR的发生剂量及临床表现进行统计分析。结果：（1）271例（72.46%）患者单独使用一种抗精神病药物,其中8例（2.14%）使用第1代抗精神病药,263例（70.32%）使用第2代抗精神病药;103例（27.54%）患者联合使用2种抗精神病药,其中7例（1.87%）联用第1代与第2代药物,96例（25.67%）联用第2代与第2代药物。（2）ADR构成比前五位的药品依次是利培酮、奥氮平、氯氮平、阿立哌唑及齐拉西酮。（3）将引发ADR的药物剂量换算成氟哌啶醇理论等价剂量,联合用药组日平均剂量为13.42±5.10 mg,单一用药组日平均剂量为6.84±3.57 mg,2组剂量差异有显著性（P<0.05）。（4）ADR临床症状主要有肌张力障碍、心慌、震颤、静坐不能及便秘;联合用药组肌张力障碍、震颤、静坐不能、流涎及泌乳ADR构成比高于单一用药组,差异有显著性（P<0.05）。结论：我院抗精神病药物治疗以单一用药为主导,联合用药发生ADR的风险更高。使用抗精神病药物治疗中应权衡利弊,谨慎增加剂量、更换药物和联合用药,并加强ADR的监测,以确保患者用药的安全性。     

8种不同非典型抗精神病药严重不良反应对比研究

目的研究8种不同非典型抗精神病药不良反应规律和特点,为临床安全合理用药提供参考。方法收集2015年1月至2019年4月浙江省上报的氯氮平、利培酮、奥氮平、喹硫平、氨磺必利、齐拉西酮、阿立哌唑和帕利哌酮导致的严重不良反应报告1497例,利用Excel软件进行统计并分析。结果非典型抗精神病药不良反应累及系统以肝胆系统损害和神经系统损害为主;不同药物呈现特有的不良反应,如帕利哌酮导致生殖系统损害、氯氮平导致胃肠系统损害、奥氮平导致血液系统损害、氨磺必利导致内分泌系统损害、阿立哌唑导致泌尿系统损害。结论各种非典型抗精神病药不良反应发生广泛,要加强不良反应监测,如定期随访肝功能和B超等。另外,应关注不同药物特有的不良反应,结合患者的基础疾病进行临床合理用药。     

Incidence and cost of adverse drug reactions in a French cancer institute

Objectives: The incidence and the cost of adverse drug reactions (ADR) in patients treated by cancer chemotherapy were assessed using hospital database records from 1993 in a French regional cancer institute. Methods: Patients with ADRs were identified using a list of ICD-9 codes describing potential adverse events. Direct medical costs for treating these ADRs were assessed according to the hospital system of claims data. Results: Among the 3429 in-patients hospitalized in 1993, we found 171 patients (5% of the population) who presented at least one ADR (3.5% of the total number of hospital stays). A total of 313 ADRs occurred in 256 hospital stays (3.5% of the hospital stays in 1993). Of the patients with ADRs 60.2% were female and their mean age was 51.5 years; 106 patients presented with at least one “serious” ADR according to the WHO definition. These ADRs occurred during 130 hospitalizations. In 7 cases, ADRs led to death. There was no relationship between age or sex and the seriousness of the ADR. Of the ADRs 91% was type “A” (predictable). We estimated that the cost of “serious” ADRs was 1.8% of the global budget of the hospital. The average cost of ADRs leading to hospitalization was 33 037 French Francs at the current rate in 1993. This cost represented an additional cost of 32% of the overall cumulative yearly cost per patient in the institution. Conclusion: This study emphasizes the medical and economic impact of the management of ADR in anticancer treatments. Received: 10 February 1997 / Accepted in revised form: 29 April 1997     

An analysis of QTc prolongation with atypical antipsychotic medications and selective serotonin reuptake inhibitors using a large ECG record database

ABSTRACT

Background: This study evaluated the effects of atypical antipsychotic drugs and selective serotonin reuptake inhibitors (SSRIs) on the corrected QT (QTc) interval using a large database obtained from clinical settings. Additionally, the effects of factors including age on QTc intervals were estimated.

Methods: Using an open-access QT database (ECG-ViEW), QTc-lengthening effects of 14 selected atypical antipsychotics and SSRIs were compared to those of a positive control drug, cilostazol, and a negative control drug, diazepam. We also evaluated effects of age, sexgender, and select electrolyte levels on observed QTc intervals.

Results: The frequency of QTc prolongation with the pooled data of the 14 study drugs was lower than that with cilostazol (age-adjusted odds ratio (OR) = 0.43, 95% confidence interval (CI) = 0.27-0.69), but no significant difference was found relative to when compared with that with diazepam (age-adjusted OR = 0.89, 95% CI = 0.55-1.47). Furthermore, administration of the 14 study drugs significantly increased the QTc interval by 2.89 ms after each 10-year age increment (p-value < 0.0001).

Conclusions: This study suggests that atypical antipsychotic drugs and SSRIs are less likely to be associated with QTc prolongation in clinical settings. In addition, age showed a significant association with the QTc interval. Further studies with well-characterized cohorts are warranted.     

Long-term pharmacotherapy for post-traumatic stress disorder

This article reviews the literature on the long-term pharmacological treatment of post-traumatic stress disorder (PTSD). A PUBMED search was conducted; only studies on the effects of long-term (>14-weeks) pharmacological treatment for PTSD in adults or children were considered. Our search identified three randomised, double-blind, placebo-controlled studies (one each for sertraline, fluoxetine and risperidone), four open-label studies (one each for sertraline, paroxetine, nefazodone and valproate), one retrospective case series (clozapine) and one pooled analysis (sertraline). All studies involved adult populations, with the exception of the study of clozapine. The studies demonstrate that long-term treatment of PTSD with SSRIs effectively maintains the previous treatment response and improvement in quality of life, converts more patients to responder status and accounts for one-third of overall treatment gains. Greater PTSD severity predicts a longer time to response to these drugs. Discontinuation of SSRI treatment after 12 weeks results in a greater risk of relapse and symptom exacerbation compared with extended treatment. In addition to improved PTSD symptoms, extended treatment with paroxetine improves verbal declarative memory and increases hippocampal volume. Long-term treatment of PTSD with atypical antipsychotics (risperidone and clozapine), non-SSRI antidepressants (nefazodone) and antiepileptic drugs (AEDs; valproate) also appears to result in significant improvements in PTSD symptoms. In conclusion, long-term treatment of PTSD with SSRIs improves the psychiatric and clinical outcome of patients with the disorder and prevents relapse and symptom exacerbation. The effect of other agents (atypical antipsychotics, AEDs and other psychotropic medications) requires further controlled study.     

Are they being used safely? A retrospective cross‐sectional tertiary health care survey of selective serotonin reuptake inhibitors prescribing practice in Singapore

OBJECTIVES: To determine the prescribing pattern of the SSRIs and to evaluate the safety of current utilization of SSRIs associated with concomitant psychotropic medications in Singapore. METHODS: The average prescribed daily dose (PDD) for each SSRI was calculated and compared with the defined daily dose (DDD). Pearson's chi2 test, one-way analysis of covariance (ANCOVA) and multinomial logistic regression were performed to examine the impacts of variables such as age, gender, patient type and concomitant psychotropic medications on the utilization of SSRIs. Safety issues were discussed by examining the potential metabolic drug interactions between the SSRIs and concomitant psychotropic medications. RESULTS: The most frequently prescribed SSRI was fluoxetine and the PDDs were slightly more than the DDDs for all these SSRIs except fluvoxamine. The SSRIs were mainly prescribed to the patients who were younger, female and outpatients. Psychotropics were more likely concomitantly used with fluvoxamine, sertraline and paroxetine, relative to fluoxetine. CONCLUSION: The prescribing pattern of SSRIs in a tertiary health center in Singapore is generally consistent with the accepted practices, although some safety concerns in terms of metabolic drug interactions were raised. This study provides useful baseline information for further in-depth studies for SSRIs usage both locally and for international comparison.     

Antipsychotic-induced Extrapyramidal Syndromes in Psychiatric Practice: A Case-control Study

Background: While several clinical trials showed that atypical antipsychotics have a low risk of extrapyramidal side effects (EPS), this observation is not undisputed. This study compared the risk of EPS between specific subgroups of antipsychotics. Methods: Using the automated dispensing records of a large psychiatric hospital in The Netherlands, we defined cases as first-time users of anticholinergic antiparkinson drugs. Controls were all patients with no recorded use of such medication. Cases and controls were compared with regard to previous use of antipsychotics and relevant co-factors. Results: Out of 1403 patients, we identified 105 cases and 330 controls. Compared to non-users, antipsychotic-users were 10 times more likely to start with anticholinergic antiparkinson medication (adjusted odds ratio: 10.1; 95 CI 4.6–22.3). Depot and non-depot antipsychotics had similar adjusted odds ratios of 10.9 (95 CI 3.7–32.6) and 8.8 (95% CI 3.8–20.4) respectively. Low and high potency antipsychotics gave odds ratios of 3.0 (95% CI 0.9–10.3) versus 10.8 (95% CI 4.7–25.1). Classical and atypical antipsychotics showed comparable odds ratios: 10.0 (95% CI: 4.4–22.5) versus 8.0 (95% CI: 2.6–24.5). Applied doses of classical and atypical antipsychotic drugs were much lower and more equivalent than those used in previous clincial trials. Conclusions: Low potency antipsychotics had a much lower risk of EPS than other antipsychotics. However, we did not corroborate the reduced risk with atypical antipsychotics observed in several clinical trials. This discrepancy may result from the high and non-equivalent doses of classical antipsychotics used in many of these trials.     

Hypothermia following antipsychotic drug use

Objective Hypothermia is an adverse drug reaction (ADR) of antipsychotic drug (APD) use. Risk factors for hypothermia in ADP users are unknown. We studied which risk factors for hypothermia can be identified based on case reports. Method Case reports of hypothermia in APD-users found in PUBMED or EMBASE were searched for risk factors. The WHO international database for Adverse Drug Reactions was searched for reports of hypothermia and APD use. Results The literature search resulted in 32 articles containing 43 case reports. In the WHO database, 480 reports were registered of patients developing hypothermia during the use of APDs which almost equals the number of reports for hyperthermia associated with APD use (n = 524). Hypothermia risk seems to be increased in the first days following start or dose increase of APs. APs with strong 5-HT2 antagonism seem to be more involved in hypothermia; 55% of hypothermia reports are for atypical antipsychotics. Schizophrenia was the most prevalent diagnosis in the case reports. Conclusion Especially in admitted patients who are not able to control their own environment or physical status, frequent measurements of body temperature (with a thermometer that can measure low body temperatures) must be performed in order to detect developing hypothermia.     

Importance of open access to atypical antipsychotics for the treatment of schizophrenia and bipolar disorder: a European perspective

ABSTRACT

Objective: To assess European psychiatrists' prescribing behaviour and their perceived need for access to a wide range of atypical antipsychotics for patients with schizophrenia and bipolar disorder.

Methods: A blinded, internet survey of psychiatrists from the UK, Germany, Italy and the Netherlands occurred in 2007. Key inclusion criteria for psychiatrists: practising full time; practising for 5–35 years; prescribed atypical antipsychotics in prior 6 months to ≥20 patients with schizophrenia or bipolar disorder. Eligible psychiatrists selected records for four patients with schizophrenia or bipolar disorder for whom they prescribed ≥1 atypical antipsychotic since January 2004.

Results: Survey response rates were: UK, 14.8% (n?=?107); Germany, 9.6% (n?=?104); Italy, 8.9% (n?=?101) and the Netherlands, 3.7% (n?=?51); 363 psychiatrists reported on 1442 patients. Psychiatrists perceived a greater difference among atypical antipsychotics as a class (mean, 5.1 on a 7-point scale [7 = ‘highly differentiated’]) but not selective serotonin reuptake inhibitors (mean, 3.6). On average, psychiatrists used 6.8 different atypical antipsychotics across their patients with schizophrenia and 4.4 across their patients with bipolar disorder, with 2.5 and 2.4 changes required following first-line treatment to stabilise therapy, respectively. The most common reason for switching medication was lack of efficacy. Psychiatrists reported that expected consequences for patients should access to atypical antipsychotics be restricted would include illness deterioration, non-adherence and hospitalisation.

Conclusions: Although this study is limited by potential selection biases, these data suggest that European psychiatrists tailor antipsychotic medications for patients with schizophrenia or bipolar disorder according to patients' needs and specific drug attributes.     

Antipsychotic drugs and short-term mortality after peptic ulcer perforation: a population-based cohort study

Background Peptic ulcer perforation is a serious surgical emergency with a substantial short‐term mortality, but the influence of antipsychotic drug use on the prognosis remains unknown. Aim To examine the association between antipsychotic drug use and 30‐day mortality following peptic ulcer perforation. Methods This cohort study comprised 2033 patients with a first‐time hospitalization with peptic ulcer perforation, in Northern Denmark, between 1991 and 2004. Data on preadmission use of antipsychotics and other medications, psychiatric disease, other comorbidities and mortality were obtained through population‐based medical databases. We used Cox regression analyses to compute adjusted mortality rate ratios (MRRs). Results One hundred and sixteen (5.7%) patients with peptic ulcer perforation were current users of antipsychotic drugs at the time of hospital admission and 205 (10.1%) were former users. The overall 30‐day mortality was 27%. Among current users of antipsychotics 30‐day mortality was 39%. The adjusted 30‐day MRR for current users of antipsychotic drugs compared with non‐users was 1.7 (95% CI: 1.2–2.3). Former use was not a predictor of mortality. The increase in mortality was equal in users of conventional and atypical antipsychotics. Conclusion Use of antipsychotic drugs is associated with substantially increased mortality following peptic ulcer perforation.     

Surveillance of adverse drug reactions at two multidisciplinary hospitals and an outpatient specialty clinic in India

Context — Adverse drug reaction (ADR) reporting is under‐developed in India, with only two of six national reporting centres currently functioning. Objective — To introduce an ADR monitoring programme at two hospitals and an outpatient skin specialty clinic in South India and to evaluate the programme. Design — An ADR monitoring programme was introduced in three participating centres and ADRs were documented and analysed over a period of six months. All unplanned admissions, all inpatients of the two participating hospitals and all outpatients of the skin specialty clinic were included in the study. A clinical pharmacist (the investigator) interviewed all patients on admission to identify suspected ADRs. For inpatients and clinic outpatients, suspected ADRs were documented by the treating doctor. A panel of four judges, including the investigator and the physician treating the patient with the suspected ADR, assessed the cases. Confirmed ADRs were then classified and categorised. Key findings — In total, 152 ADRs were documented. The percentage of patients with a reported ADR at each of the three centres was 3.5, 3.7 and 2.3. The gender of patients with reported ADRs was 53.9 per cent male and 46.1 per cent female. Most of the patients had a type “A” reaction (110, 72.4 per cent). Using Naranjo's probability scale, 25.7 per cent of ADRs were categorised as “probable” and 74.3 per cent as “possible.” Of the ADRs reported in the two hospitals, 31.1 per cent related to unplanned medication‐related hospital admissions and 68.9 per cent occurred during the hospital stay. Antibiotics (32.2 per cent), psychotropic drugs, steroids and non‐steroidal anti‐inflammatory drugs (11.8 per cent each) were the most common drugs that caused ADRs. General medicine (37.5 per cent) and dermatology (35.5 per cent) departments accounted for the highest number of ADRs. Pruritic rash (36.7 per cent) was the most common ADR reported at the skin clinic while pruritic rash, gastritis and diarrhoea (10.7 per cent each) and akathisia and hypoglycaemia (7.8 per cent) were the most common ADRs reported in the hospitals. Conclusion — This is the first study to evaluate an ADR reporting programme in India. Introduction of the ADR monitoring programme improved health care practitioners' awareness of the importance of pharmacovigilance. Occurrence of ADRs seemed to be similar to those reported in the developed world, with the exception of the proportion of severe ADRs (25 per cent), which was higher than reported elsewhere in published studies.     

SSRI treatment decreases prolactin and hyperthermic responses to mCPP

We studied the effect of 3 weeks treatment with the selective serotonin re-uptake inhibitor (SSRI), paroxetine (30 mg daily), on the neuroendocrine and hyperthermic responses to the 5-HT_2C receptor agonist, m-chlorophenylpiperazine (mCPP) (0.05 mg/kg IV), in seven healthy volunteers. Following paroxetine treatment, both the prolactin and hyperthermic responses to mCPP were significantly attenuated. These data are consistent with experimental animal studies indicating that repeated SSRI treatment leads to a functional desensitisation of 5-HT_2C receptors. This effect may be linked to the anxiolytic properties of SSRIs. Received: 2 May 1997/Final version: 30 June 1997