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ORIGINAL ARTICLE
Year : 2012  |  Volume : 2  |  Issue : 2  |  Page : 135-141

Pharmacoepidemiological study of antipsychotics in the psychiatry unit of a tertiary care hospital: A retrospective descriptive analysis


1 Department of Pharmacology, Therapeutic Community and Unity House, London, United Kingdom
2 Core Trainee in Psychiatry 2, SHO in Psychotherapy, Therapeutic Community and Unity House, London, United Kingdom
3 Department of Psychiatry, Mahatma Gandhi Medical College and Research Institute, Pondicherry, India

Date of Submission03-Apr-2011
Date of Acceptance27-Jun-2011
Date of Web Publication9-May-2012

Correspondence Address:
Kingshuk Lahon
Department of Pharmacology, Mahatma Gandhi Medical College and Research Institute, Pondicherry 607 402
United Kingdom
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/2231-0738.95982

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   Abstract 

Aims: Pharmacoepidemiology is an interface discipline that studies the interactions between drugs and populations. Pharmacoepidemiological studies reveal the differences that exist between the conditions of premarketing trials (done on a limited sample population) and those of actual practice. Antipsychotic prescribing patterns have changed globally over the last few years. Hence, we wanted to observe the prescribing pattern of antipsychotics in our hospital and assess the rationality of the prescriptions and the prevalence of antipsychotic usage in the community. Materials and Methods: This was a retrospective observational analysis of case records of patients receiving antipsychotic prescriptions in the psychiatry outpatient clinic of a tertiary care hospital during the period 1 st January 2006 to 31 st December 2006. We studied the following parameters: Antipsychotic drugs prescribed, completeness and rationality of prescriptions, WHO prescribing indicators, defined daily dose (DDD)/1000/day (DID), prescribed daily dose (PDD), and the PDD to DDD ratio. Results: Antipsychotics were prescribed in 32.88% patients (olanzapine: 65.66%, risperidone: 19.19%, aripiprazole: 7.07%, others: 8.08%). The average number of drugs/prescription: 2.19, prescribing by generic names: 63.64%, prescribing from WHO essential medicines list (EML) and injections: 3.03%. There were no prescriptions for fixed-dose combinations (FDC). DID of antipsychotics: 0.0008 mg. PDD to DDD ratios <1 for quetiapine and haloperidol, while for others it was ≥1. Conclusion: The second-generation antipsychotics olanzapine, risperidone, and aripiprazole were the most commonly prescribed antipsychotics. Prescriptions were complete and without polypharmacy. Favorable and unfavorable outcomes were seen for two and three WHO prescribing indicators, respectively. Antipsychotic consumption in the community was low. Adequate dosing was seen for all antipsychotics, except quetiapine and haloperidol (where there was underdosing). Choosing drugs from the EML-based hospital formulary will decrease cost of therapy and promote rational use of medicines.

Keywords: Antipsychotics, drug utilization, defined daily dose, prescribed daily dose


How to cite this article:
Lahon K, Shetty HM, Paramel A, Sharma G. Pharmacoepidemiological study of antipsychotics in the psychiatry unit of a tertiary care hospital: A retrospective descriptive analysis. Int J Nutr Pharmacol Neurol Dis 2012;2:135-41

How to cite this URL:
Lahon K, Shetty HM, Paramel A, Sharma G. Pharmacoepidemiological study of antipsychotics in the psychiatry unit of a tertiary care hospital: A retrospective descriptive analysis. Int J Nutr Pharmacol Neurol Dis [serial online] 2012 [cited 2019 Sep 21];2:135-41. Available from: http://www.ijnpnd.com/text.asp?2012/2/2/135/95982


   Introduction Top


Pharmacoepidemiology is an interface discipline that studies the interactions between drugs and populations. [1] Application of pharmacoepidemiological studies often reveals the large differences that exist between the conditions of premarketing trials (done on a limited sample population) and those of actual practice several years into the market life of a pharmaceutical product. [2] Clinical trial data must therefore be complemented by measurement of any eventual distortions and estimation of the real-life effectiveness and safety of the medicines.

The gap between guidelines and prescribing pattern is well established for antipsychotic drugs. [3] Pharmacoepidemiological studies are necessary to identify possibly unfounded or hazardous extensions of the indications for psychotropic medications. Prescribing patterns of antipsychotic drugs have changed worldwide, with conventional antipsychotics being replaced by new-generation atypical agents.

Therefore, we wanted to study the utilization of antidepressant drugs in the psychiatric unit of a tertiary care hospital in Pondicherry. Our objectives were:

  1. To observe the prescribing pattern of antipsychotics
  2. To assess the rationality of the prescriptions
  3. To assess the prevalence of antipsychotic usage in the community

   Materials and Methods Top


We conducted a retrospective observational study of case records in the psychiatric unit of a tertiary care hospital in Pondicherry during the period 1 st January 2006 to 31 st December 2006. Data were entered in a predesigned proforma [Table 1].
Table 1: Data collection sheet/proforma

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Inclusion criteria

  1. All patients who attended the psychiatry outpatient clinic of the hospital from 1 st January 2006 to 31 st December 2006.
  2. All patients diagnosed with psychosis (diagnosed as per International Classification of Diseases (ICD)-10 criteria) [4] or any condition where antipsychotics are indicated.
Exclusion criteria

  1. Patients who did not receive antipsychotic drugs.
  2. Patients only continuing antipsychotic drugs prescribed from elsewhere.
Following the method of Baldessarini et al. [5] for defining drug use, we took all prescriptions from the case records containing at least one antipsychotic drug as one prescription. Any dose change for the antipsychotic in that prescription was calculated for consumption data. Addition of another antipsychotic to, or change of antipsychotic from the existing regimen, was regarded as a separate prescription. In both cases, the number of drugs in the prescription included the added or changed antipsychotic(s), along with the concomitant medications. However, prescriptions containing drugs for comorbid (nonpsychiatric) conditions, which were not prescribed in the department of psychiatry, were excluded.

Data analysis

Data were subjected to analysis for:

  1. Demographic details (age and gender)
  2. Psychiatric diagnosis
  3. Antipsychotic drugs prescribed and prescribing pattern
  4. Completeness of prescription, appropriateness of drug, dose, frequency, and duration
  5. Rationality of prescriptions according to WHO prescribing indicators
  6. Defined daily dose (DDD) of the antipsychotics per thousand inhabitants per day (DID)
  7. Prescribed daily dose (PDD) of the antipsychotics
  8. PDD to DDD ratio of the antipsychotics
We applied anatomical therapeutic chemical (ATC) classification and defined daily dose (DDD) per thousand inhabitants per day (DID) and prescribed daily dose (PDD) calculations for estimating antipsychotic use in the community.

Following the methodology outlined by WHO, [6] we calculated DID using the population of the Union Territory of Pondicherry and Cuddalore district of Tamil Nadu, India (because all patients came from these areas) as per available census data.

By adding up the DIDs for individual antipsychotics, we derived the number of DIDs for the antipsychotics as a whole.

PDD was calculated as follows: For each prescription, dose titrations resulted in multiple doses of the antipsychotics, and so we took the average of the daily doses for the antipsychotic as the PDD. This process was repeated for all indications of each antipsychotic drug until we got the final value as the average of the PDDs thus obtained.

PDD to DDD ratio was then calculated.

Statistical analysis

Descriptive statistical tools were used.

Ethical clearance

As this was a noninterventional study, the institutional research committee granted a waiver on the assurance that subject confidentiality would be maintained.


   Results Top


Out of 222 patients receiving psychotropic medicines during the study period, 73 received one or more antipsychotics (32.88%). Among these 73 patients, 35 (47.95%) were males and 38 (52.05%) were females. Age distribution is shown in [Table 2].
Table 2: Age distribution of patients prescribed antipsychotics

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The distribution of primary psychiatric diagnoses of patients receiving antipsychotics is shown in [Table 3].
Table 3: Primary ICD-10 psychiatric diagnoses of patients receiving antipsychotics

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The total number of prescriptions given was 99, and a total of 217 drugs were prescribed. Of them, 99 were antipsychotic medications of seven types (as per ATC class). [Table 4] shows the different antipsychotics prescribed. The number of antipsychotic prescriptions, along with their indications, is shown in [Table 5].
Table 4: Prescribing frequency of antipsychotic drugs

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Table 5: Indications for antipsychotics used

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All prescriptions contained the patient's primary diagnosis, drug(s) prescribed, dosage form, dose, frequency of administration, and duration of treatment, along with the dates of follow-up. No instance of inappropriate prescribing of antipsychotic drugs or of use of wrong dose, frequency, or duration of treatment was observed. However, all patients did not come for regular follow-up.

Only one antipsychotic was initially prescribed for each patient. Change of antipsychotic was required on five occasions. Haloperidol was substituted on three occasions and olanzapine and risperidone on one occasion each. Addition of a second antipsychotic was seen on nine occasions because of poor response with a single drug. A third antipsychotic drug was added to the existing two-drug regimen in one case of refractory schizophrenia.

[Table 6] shows concomitant medications that were prescribed in the department of psychiatry. [Table 7] shows the number of drugs per prescription among the 99 prescriptions. No patient was prescribed more than five drugs in a single prescription.
Table 6: Concomitant medications prescribed with antipsychotics

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Table 7: Distribution of number of drugs per prescription

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As per WHO prescribing indicators, we observed the following:

  • Average number of drugs per prescription: 2.19 (217/99)
  • Percentage of antipsychotic drugs prescribed by generic name: 63.64% (63/99 × 100)
  • Percentage of fixed-dose combinations of antipsychotics: Nil
  • Percentage of encounters for prescribing injections of antipsychotics: 3.03% (3/99 × 100)
  • Percentage of antipsychotic drugs prescribed from WHO essential medicines list (EML): 3.03% (3/99 × 100)
The percentage of antipsychotic drugs prescribed from the national list of essential medicines (NLEM, endorsed 2002) was 93.93% (93/99 × 100).The percentage of drugs prescribed from the hospital formulary was 3.03% (3/99X 100).

The ATC coding and calculation of DID and PDD are summarized in [Table 8]. The total number of DIDs of antipsychotics was 0.0008.
Table 8: ATC/DDD classification with calculated DDD/1000 inhabitants/day, PDD values of prescribed antipsychotics and PDD/DDD ratio

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The PDD and the PDD to DDD ratios are also summarized in [Table 8].


   Discussion Top


Antipsychotics were the second most commonly prescribed medicines after antidepressants in our psychiatric outpatient clinic. We observed a higher prevalence of antipsychotic prescribing in females compared to males. This female preponderance is similar to the findings of a Western study on the epidemiology of antipsychotic drug usage. [7] The majority of patients, receiving antipsychotics belonged to the 21-30 years age-group (42.47%). In fact, 67.13% were aged between 21 and 40 years. This contrasts with the findings of a European study wherein the mean age of patients receiving antipsychotics was over 40 years. [8] In another study, antipsychotic prescribing was greater in males between 25-55 years and in women 75 years and above. [9]

Schizophrenia was the most common psychiatric diagnosis among the population (n=222), with a prevalence of 43.84%. It was also the most common indication for using antipsychotics (52.53% of antipsychotic prescriptions). Depressive disorder and bipolar affective disorder (BPAD) were the other common diagnoses.

Most common antipsychotic prescribed was olanzapine (65.66%). The second generation antipsychotics - olanzapine, risperidone, aripiprazole, quetiapine, and ziprasidone accounted for the bulk of prescriptions (95.96%), which is similar to the findings of other studies. [9],[10],[11],[12] The doses of antipsychotics were tailored to the severity of the disease/disorder: The drugs were started at low doses and titrated upward or downward according to clinical response, and the patients were followed up at regular intervals.

Olanzapine was the most common antipsychotic prescribed in schizophrenia (51.92%), depressive disorder (78.26%), and BPAD (76.92%). The prescribing of antipsychotics in schizophrenia follows the trend seen in an earlier Australian study [13] but contrasts with the results of a study in Malaysia in an outpatient setting, wherein the conventional antipsychotics haloperidol and zuclopenthixol were the most common drugs prescribed. [14]

Prescription of a single antipsychotic was common and monotherapy was found in 84 out of 99 (84.85%) antipsychotic prescriptions, which contrasts with the findings of many cross-sectional surveys where antipsychotic polypharmacy is common, especially in schizophrenia. [15] The reasons for changing an antipsychotic were poor therapeutic response or intolerable adverse effects. Injections of haloperidol and zuclopenthixol were administered only as an emergency intervention to treat acute psychotic states.

Sedative hypnotics (53.53%) were the most common group of drugs prescribed concomitantly with antipsychotics. Other concomitant medications were antidepressants, mood stabilizers (valproic acid), trihexiphenidyl, acamprosate, thyroxine, and propranolol. Except for thyroxine (which was prescribed in depressive disorders) and propranolol (which was prescribed for treatment of tremors) all the other concomitantly prescribed drugs were psychotropic medications. Trihexiphenidyl was prescribed to counter the extrapyramidal adverse effects of antipsychotics.

Rational prescribing was followed as per the principles of prescription order writing. [16] Definitions of polypharmacy that are most commonly cited are the prescribing of medication not matching the diagnosis and presence of more than six drugs in a single prescription. [17] As per these criteria, there was no polypharmacy as no inappropriate drug was prescribed and no prescription contained more than five drugs. Among the prescriptions, 49.49% (49/99) had two drugs or less, which is the recommended figure. The clinicians' choice of drug was not based on the cost and so the cheapest drug was not always prescribed.

The average number of drugs per prescription was more than two, which is high. Prescribing by generic names was high (88.54%) There were no fixed-dose combinations (FDCs) prescribed and the percentage of encounters for injections was low (3.03%), which indicate rational prescribing practices. The percentage of drugs prescribed from the 16 th WHO EML and from the hospital formulary was low, but prescribing as per NEML (endorsed 2002) was high. This indicates the need to bring about a balance between clinicians' requests for keeping a drug in the hospital formulary and the recommendations of the NEML.

The ATC classification system divides drugs into different groups according to the organ or system on which they act and their chemical, pharmacological, and therapeutic properties. [18],[19] Each drug is assigned a particular combination of letters and numbers. The DDD is the assumed average maintenance dose per day for a drug used for its main indication in adults. [15] The DDD was developed to overcome objections against traditional units of measurement of drug consumption and to ensure comparability between different drug utilization studies.

The total DID of the antipsychotics showed low consumption. A 10-year database study of antipsychotic utilization in the US showed relatively high consumption rates, [20] but a study conducted in Eastern Europe showed declining trends of consumption, even though the utilization was much higher than in our study. [21]

The DID for olanzapine can be interpreted as 0.0002 out of 1000 patients, i.e., 0.00002% would have used a dose of 10 mg. Similarly, the DIDs of risperidone, aripiprazole, quetiapine haloperidol, ziprasidone, and zuclopenthixol can be interpreted as consumption of their respective DDDs by a population of 0.00004%, 0.00002%, 0.0000007%, 0.00000000001%, 0.000002%, and 0.000002%.

The PDD is defined as the average dose prescribed according to a representative sample of prescriptions. It is important to relate the PDD to the diagnosis on which the dosage is based. The PDD denotes the average daily amount of a drug that is actually prescribed. PDD is especially important for drugs where the recommended dosage differs from one indication to another (e.g., psychotropic drugs). When there is a substantial discrepancy between the PDD and the DDD, we must take this into consideration when evaluating and interpreting drug utilization figures, particularly in terms of morbidity.

Ratio of PDD to DDD is often used as an indication of the adequacy of dosing. For quetiapine and haloperidol the ratio was <1, which indicates underdosing. All other antipsychotics showed a PDD to DDD ratio ≥1, reflecting the adequacy of dosing. [22]

Limitations of the study

Our study had a relatively small sample size and the results should be viewed in that light. The limitations of the study were the lack of patient care indicators and some of the facility indicators (such as availability of drugs and impact of cost on drug treatment), which would have increased the utility of the study, but these can only be derived prospectively. As with any drug-utilization study, it was not possible to monitor actual use or compliance with prescribed antipsychotics, more so with a retrospective study of case records, where notes on compliance are lacking.

Strengths of the study

The strengths of the study are the use of a structured proforma for data collection, with details of drug prescriptions on follow-up visits, and a comprehensive application of drug utilization tools like ATC/DDD classification and calculation of DID and PDD/DDD ratios to assess prevalence of antidepressant use in the study population. Documentation of longitudinal follow-up data gives a better idea of drug consumption than cross-sectional data. Data on drug substitutions and augmentations as well as concomitant psychotropic medications are also provided.


   Conclusion Top


Our study shows that schizophrenia is the most common psychotic disorder in this population. There was a higher prevalence of antipsychotic prescribing for women. The majority of antipsychotics were prescribed to young and older adults between 21 and 40 years. The second generation antipsychotics olanzapine, risperidone, and aripiprazole were the most commonly prescribed antipsychotics, with or without other concomitant psychotropic medicines. Most patients were treated with a single antipsychotic. However, poor response and/or tolerability considerations made the prescribers change the antipsychotic or add a second antipsychotic. Antipsychotics were prescribed for many indications other than schizophrenia and the psychiatrists' choice of drug was influenced by diagnosis, severity of disease/disorder, co-morbidity, drug efficacy, and considerations for patients' tolerability, but not primarily by the cost of medication. Prescriptions were complete and polypharmacy was not seen. Favorable and unfavorable outcomes were seen for two and three WHO prescribing indicators, respectively. Consumption of antipsychotics in the community was low. Adequate dosing was seen for all antipsychotics, except for quetiapine and haloperidol, for which underdosing was prevalent.

There is a need for prospective drug-utilization studies to overcome some of the limitations of our study. Prescribing habits among psychiatrists can be improved further by incorporating more drugs from the Hospital Formulary, which should model itself on the National and WHO EML. Such measures can decrease the cost of therapy. Prescribers should also be encouraged to check for patients' compliance with the prescribed medications and to record them in the case sheets. This will promote the rational use of medicines and ultimately, the quality of health care.

 
   References Top

1.Begaud GB. Dictionary of Pharmacoepidemiology. Chichester: John Wiley and Sons; 2000.  Back to cited text no. 1
    
2.Martin K, Bégaud B, Latry P, Miremont-Salame G, Fourrier A, Moore N. Differences between clinical trials and post-marketing use. Br J Clin Pharmacol 2004;57:86-92.  Back to cited text no. 2
    
3.Barbui C, Danese A, Guaiana G, Mapelli L, Miele L, Monzani E, et al. Prescribing second-generation antipsychotics and the evolving standard of care in Italy. Pharmacopsychiatry 2002;35:239-43.  Back to cited text no. 3
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4.World Health Organisation. The ICD-10 Classification of Behavioural and Mental Disorders. Diagnostic criteria for research. Geneva: World Health Organisation; 1993. Available from: http://www.who.int/classifications/icd/en/GRNBOOK.pdf. [Last accessed on 2010 Dec 6].  Back to cited text no. 4
    
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6.WHO Collaborating Centre for Drug Statistics Methodology. Guidelines for defined daily doses. Oslo: WHO Collaborating Centre for Drug Statistics Methodology; 1991.  Back to cited text no. 6
    
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18.WHO Collaborating Centre for Drug Statistics Methodology. Guidelines for ATC classification and DDD assignment. Oslo: WHO Collaborating Centre for Drug Statistics Methodology; 2002.  Back to cited text no. 18
    
19.WHO Collaborating Centre for Drug Statistics Methodology. ATC index with DDDs. Oslo: WHO Collaborating Centre for Drug Statistics Methodology; 2002.  Back to cited text no. 19
    
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22.Smalbrugge M, Jongenelis LK, Pot AM, Beekman AT, Eefsting JA. Pain among nursing home patients in the Netherlands: Prevalence, course, clinical correlates, recognition and analgesic treatment - an observational cohort study. BMC Geriatr 2007;7:3  Back to cited text no. 22
    



 
 
    Tables

  [Table 1], [Table 2], [Table 3], [Table 4], [Table 5], [Table 6], [Table 7], [Table 8]



 

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