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Polypharmacy in patients with schizophrenic disorders treated in a psychiatric outpatient care unit

Bernd Rüdiger Brüggemann1, Marc Ziegenbein1§ , Hermann Elgeti1

1Department of Social Psychiatry and Psychotherapy, Hannover Medical School,

30623 Hannover, Germany

§Corresponding Author:

Marc Ziegenbein, MD

Department of Social Psychiatry and Psychotherapy

Hannover Medical School (MHH), OE 7120

Carl-Neuberg-Str. 1

D-30625 Hannover

Abstract

Background. We investigated the frequency and type of polypharmacy in patients with a schizophrenic disorder at the Psychiatric Outpatient Care Unit of the Hanover Medical School.

Methods. The last medication of the year was recorded for all patients treated in 2005 for a schizophrenic disorder (N = 172). In the further evaluations, only patients were included who were prescribed medication in our outpatient care unit (n = 136).

Results. On average, patients received 2.1 psychotropic drugs. 64 % received a combination therapy. 65% of the patients received an atypical antipsychotic drug, and 40 % a conventional high-potency antipsychotic drug. Conventional high-potency antipsychotics were combined in 18 % of the patients with a low-potency antipsychotic drug, in 12% with an anticholinergic, in 7 % with a mood stabilizer and in 6 % with an atypical antipsychotic drug. Atypical antipsychotics were combined in 23 % of the patients with a low-potency antipsychotic drug, in 9 % with an anticholinergic, in 10 % with a mood stabilizer and in 7 % with an additional atypical antipsychotic.

Conclusions. Among patients with a schizophrenic disorder treated in the outpatient care unit, polypharmacy is more the rule than the exception, and various drug classes are of importance. When polypharmacy becomes necessary, it should only be administered, whenever possible, according to evidence-based data or at least after a good deal of rational consideration given to pharmacokinetic and dynamic interactions. Due to the widespread use of polypharmacy in psychiatry, there is an urgent need for controlled studies further investigating combinations of substances.

Background

The current therapeutic guidelines of the large psychiatric professional societies recommend first implementing monotherapy for nearly all psychiatric disorders in the event of psychotropic drug treatment. Contrary to the recommendation only to administer one substance in the optimal dosage, clinical practises very frequently administer combination therapies which often are substantiated by little or no scientific evidence. Stahl aptly described the discrepancy between the evidence-based recommendations and the actual practise as “the dirty little secret” of psychiatry [1].

In the treatment of patients with schizophrenic disorders, this discrepancy becomes particularly clear where combination therapy is the rule in clinical practise. Therapy may include combinations of several anti-psychotic drugs as well as the combination of anti-psychotics with psychotropic drugs from other drug classifications (including anti-depressants, mood stabilizers, anxiolytics/hypnotics) [2]. In this regard, an increase has been determined in the use of combination treatment [3;4]. Indeed among therapy-resistant affective disorders, a growth in polypharmacy has also been noted [5]. The frequency of polypharmacy increases with the length and severity of the illness [6]. Despite insufficient scientific evidence, polypharmacy may be advisable once other options for therapy – such as psychotherapy, socioenvironmental therapy and complementary support – have been exhausted. This is especially true in the presence of comorbidity with an additional mental disorder. On the other hand, problematic combinations and combinations deemed irrational for theoretical reasons can be avoided based on drug interactions and side effects [2].

The present study investigates the frequency and type of polypharmacy in patients with schizophrenic disorders at the psychiatric outpatient care unit in the Department of Social Psychiatry and Psychotherapy at the Hanover Medical School.

The psychiatric outpatient care unit of the HMS provides the care for a region of Hanover, a catchment area of approximately 62,000 residents near the city centre. The team includes 17 staff members from five occupational groups covering 11.8 full-time positions and integrating two different care programmes: Initial contact and short-term crisis intervention take place at the social-psychiatric service of the polyclinic. The psychiatric outpatient care unit carries out long-term, continuous, multidiscinplinary treatment programmes.

Methods

Patients’ medical records were used to collect data on the last medication prescribed in the year for the entire group of patients with a schizophrenic disorder treated in 2005 (N = 172). Since some patients were prescribed medication by a physician in private practise, for the further evaluations we only included patients whose medication was prescribed in our outpatient care unit (n = 136).

Results

Between 1 and 6 psychotropic drugs were prescribed. On average, patients received 2.1 psychotropic drugs. 36 % received a monotherapy and 64 % a combination therapy. The following drug classes were prescribed: atypical antipsychotics 65 %, conventional high-potency antipsychotics 40 %, depot antipsychotics 18 %, low-potency antipsychotics 37 %, anti-depressants 10 %, mood stabilizers 17 %, tranquilizers 7 %, anticholinergics 16 % (see Figure 1). Conventional high-potency antipsychotics combined in 18 % of the patients with a low-potency antipsychotic drug, in 12 % with an anticholinergic, in 7 % with a mood stabilizer and in 6 % with an atypical antipsychotic drug. Atypical antipsychotics were combined in 23 % of the patients with a low-potency antipsychotic drug, in 9 % with an anticholinergic, in 10 % with a mood stabilizer and in 7 % with an additional atypical antipsychotic drug. In all patients who received a combination therapy (n = 89), an antipsychotic drug was involved. Even in patients who already were receiving an antipsychotic drug, an addition antipsychotic was the most frequent combination partner, followed by the mood stabilizers and anti-depressants (see Table 1).

Table 1: Score of substance combinations according to drug group in patients with a schizophrenic disorder who received a combination therapy (n=87)

Drug groups	Treated patients	Drugs used for Coadministration
Drug groups	Treated patients	AP	AD	PP	TQ
AP	87	69 %	16 %	25 %	10 %
AD	14	100 %	14 %	43 %	14 %
PP	22	100 %	27 %	0 %	5 %
TQ	9	100 %	22 %	11 %	0 %

AP: Antipsychotic, AD: Antidepressant, PP: Mood stabilizer, TQ: Tranquilizer/Hypnotic

Discussion

Despite the lack of evidence, polypharmacy is common practice in psychiatry. Doubtlessly the possibilities of monotherapy should first be exhausted, meaning a single drug should be administered in sufficient dosage over a sufficiently long period of time, and the patient’s compliance should be encouraged and, as necessary, monitored by determining the serum plasma levels. When polypharmacy becomes necessary, it should, whenever possible, be implemented according to evidence-based data or at least rational consideration with regard to pharmacokinetic and dynamic interactions. The vast number of drugs available for treatment can make it difficult for physicians to maintain in-depth knowledge of all drug interactions, therefore they should rely on appropriate medical databases. For adequate pharmacological treatment, it is of utmost importance that the type, dose and length of treatment is documented in correlation to the clinical changes. Even increased awareness of the problem of polypharmacy and corresponding educational programmes can help reduce the practise [7-9].

The frequency of polypharmacy has been investigated both in outpatients [3;10-14] and inpatients [15-19]. These studies generally focused on the combination of antipsychotics in patients with schizophrenic disorders. The combination with low-potency antipsychotics and with medications from other drug classes has largely been disregarded. In their review article, Messer et al. find that 40-50 % of schizophrenic patients requiring inpatient treatment and up to 90 % of the outpatients receive an antipsychotic combination therapy [2].

A study investigated the year 1998 on the prescription of antipsychotic drugs and co-medications in an Australian community psychiatric service bearing a close resemblance in structure to our outpatient care unit [20]. Of the 859 patients included in the study, 77% received an antipsychotic medication. The percentage of atypical antipsychotic drugs was 53 %. Patients who were administered a conventional antipsychotic drug, received it in 66 % of the cases as a depot antipsychotic. 13 % received a combination therapy of antipsychotics, most frequently including a combination of an atypical with a conventional antipsychotic in 8% of the cases. Investigations into the patterns of drug prescription in psychiatric outpatient care units in the German-speaking world do not exist as far as we know.

A large portion of the schizophrenic patients we treated received psychopharmacological medication. When psychopharmacological drugs were prescribed, they mostly were part of a combination therapy. Atypical antipsychotics were prescribed considerably more frequently than conventional antipsychotics. Among antipsychotics, administered in depot form, the conventional antipsychotics clearly dominated. This is due to the fact that a large part of the patients receiving the depot drug had been taking it for many years, were well-adjusted to it and tolerated it well.

The drug combinations showed antipsychotics to occupy a special role. The combination of an atypical antipsychotic with a high-potency conventional antipsychotic or another atypical antipsychotic can be advisable in the presence of therapy resistance in monotherapy or to reduce side effects of a high-dose monotherapy. In these cases, pharmacokinetic and dynamic interactions must be taken into account [2]. Anti-depressants can be usefully combined with antipsychotics in the presence of a schizo-affective disorder or comorbidity of a depressive disorder with a schizophrenic psychosis. The combination of antipsychotics with mood stabilizers usually is prescribed in schizo-affective disorders and can be advisable in the context of therapy-resistant schizophrenic disorders. Mood stabilizers and tranquilizers were almost always prescribed as co-medication in our sample in combination with an additional psychotropic drug.

As the number of prescribed psychotropic drugs increases, the pharmacokinetic and dynamic interactions grow more complex and the danger of sometimes hazardous side effects increases as well. Furthermore, the interactions with medications that have been prescribed due to somatic comorbidity must also be taken into account. In addition to rational therapy considerations, other reasons can also lead to polypharmacy. In some instances a combination therapy is maintained when the transition phase from one medication to another shows improvement and this improvement is not clearly attributable to the new medication or the combination thereof. Moreover, initial combination therapies that were necessary due to an exacerbation of a schizophrenic disorder during inpatient care may be continued in outpatient care. To some extent this might be connected to irrational fears on the part of the attending physician and patients concerned that a change in medication could lead to a relapse. The magnitude of polypharmacy in our study can also be explained in part by the fact that the chronically and severely ill patients treated in our outpatient care unit belong to a high-risk population due to therapy resistance and comorbidities, and for whom a polypharmacy of psychotropic substances may be advisable. In any event, there was no significant reduction in combination treatments from the first half to the second half of 2005, despite several in-house training sessions designed to address this issue.

Due to the widespread use of polypharmacy in psychiatry, further investigations into drug combinations within the framework of controlled studies are urgently needed in the future.

Conclusions

Among patients with a schizophrenic disorder treated in the outpatient care unit, polypharmacy is more the rule than the exception, and various drug classes are of importance. The magnitude of the polypharmacy in the patients from our sample can be explained in part by the fact that these chronically and severely ill persons belong to a high risk population due to their resistance to therapy and comorbidity. When polypharmacy becomes necessary, it should only be administered, whenever possible, according to evidence-based data or at least after a good deal of rational consideration given to pharmacokinetic and dynamic interactions. Due to the widespread use of polypharmacy in psychiatry, there is an urgent need for controlled studies further investigating combinations of substances.

Competing interests

The authors declare that they have no competing interests.

Authors' contributions

BRB and HE conceived and designed the evaluation and helped to draft the manuscript. MZ re-evaluated the clinical data and revised the manuscript. BRB and HE collected the clinical data and interpreted them. All authors read and approved the final manuscript.

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First Published November 2007

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