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REVIEW ARTICLES |
North Wales Section of Psychological Medicine, Wrexham Academic Unit, Technology Park, Wrexham, Wales, UK
Institute of Medical and Social Care Research, University of Wales Bangor, Gwynedd, Wales, UK
Department of Psychiatry, University of Ulm, Ulm, Germany
Correspondence: Dr Peter Lepping, North Wales Section of Psychological Medicine, Wrexham Academic Unit, Technology Park, Wrexham, LL13 7YP, UK. Email: peter.lepping{at}new-tr.wales.nhs.uk
Declaration of interest P.L. has received fees from Lilly, Otsuka and AstraZeneca for educational talks.
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ABSTRACT |
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Aims To evaluate the effectiveness of typical and atypical antipsychotics in primary delusional parasitosis (delusional disorder, somatic type).
Method A systematic review was conducted.
Results No randomised trials were found and hence we collected the best evidence from 16 other trials and case reports, separating primary from other forms of delusional parasitosis. Studies using typical antipsychotics showed partial or full remission in between 60 and 100% of patients. Analysis of selected patients with primary delusional parasitosis showed that typical and atypical antipsychotics were effective in the majority, but that remission rates did not differ significantly between typical and atypical antipsychotics.
Conclusions In the absence of controlled trials there is limited evidence that antipsychotics are effective in primary delusional parasitosis. Rigorous studies are needed to evaluate their effectiveness and to compare typical and atypical antipsychotics directly.
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INTRODUCTION |
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History |
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Pathogenesis |
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Clinical management |
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Another approach to achieve a better therapeutic relationship was developed in the late 1980s. Specialised out-patient clinics were located in dermatology clinics to acknowledge the patients' non-psychiatric concept of their illness (Musalek & Kutzer, 1989; Musalek et al, 1989; Musalek, 1991; Trabert, 1993). However, even these `low threshold' settings have often failed to allow the establishment of a sufficient therapeutic alliance. Trabert's study in Homburg, Germany stated that 20 of 35 patients (57%) were seen for less than 3 months (Trabert, 1993). Despite all these efforts, many patients lose faith in professional medicine and resort to dangerous self-therapies such as excessive skin cleaning with chemicals or pesticides (Freudenmann, 2002).
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Antipsychotic treatment |
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Several case reports have indicated the beneficial effects of atypical antipsychotics in primary delusional parasitosis, but evidence for these is still limited to risperidone (Gallucci & Beard, 1995; Freyne et al, 1999; Moretti & Varga, 2000), quetiapine (Kim et al, 2003), olanzapine (Le & Gonski, 2003) and amisulpride (Lepping et al, 2005).
Although it is often stated that there is a lack of randomised controlled trials of the use of antipsychotics (including pimozide) in delusional parasitosis (Driscoll et al, 1993; Trabert, 1995; Freudenmann & Schönfeldt-Lecuona, 2005), we know of no systematic review on this topic. Moreover, no antipsychotic is licensed for the treatment of delusional parasitosis. We therefore undertook the first systematic review of the effectiveness of typical and atypical antipsychotic treatment for primary delusional parasitosis (meeting ICD–10 F22.0 criteria for persistent delusional disorder or DSM–IV–TR criteria for delusional disorder of somatic type) in order to determine whether: typical antipsychotics are effective in treating primary delusional parasitosis and are more effective than placebo; atypical antipsychotics are effective in treating primary delusional parasitosis and more effective than placebo; atypical antipsychotics are more or less effective than typical antipsychotics.
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METHODS |
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Assessment of literature
P.L. and R.W.F. independently assessed whether all retrieved works dealt
with delusional parasitosis in general or primary delusional parasitosis, and
whether the intervention consisted of typical or atypical antipsychotics. We
also assessed whether any of these were randomised controlled trials.
In the absence of randomised controlled trials we planned to gather sound evidence from other studies meeting defined inclusion criteria (see Appendix 2). In particular we sought well-designed quasi-experimental and observational studies relevant to our research questions. We included all open studies with either prospective design or more than 30 patients. We then summarised in structured form the main findings of the 16 studies meeting these minimal criteria (Table DS1, data supplement to online version of this paper). We assigned individual outcomes between three main categories: no effect (0); partial remission (i.e. some response) (1) and full remission (2). To strengthen our conclusions we also tried to separate primary delusional parasitosis from secondary delusional parasitosis.
P.L. and R.W.F. also selected all case reports containing information on diagnosis of primary delusional parasitosis, gender, age, antipsychotic medication used and dose, and clinical outcome on the same 3-point scale after 4 weeks or more. In this way we applied Trabert's case-based meta-analysis which is designed for uncommon syndromes that cannot be studied in a traditional randomised controlled trial (Trabert, 1995). We also separated patients treated with typical and atypical antipsychotics. Although this approach is subject to publication bias because it considers only published cases, we aimed to increase comparability between studies. To judge the success of this strategy we tested whether clinical outcomes differed significantly between studies.
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RESULTS |
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Absence of randomised controlled trials
Our systematic search found no randomised controlled trials on the
effects of typical or atypical antipsychotics in either primary or other
delusional parasitosis. When accessed in December 2005, the Clinical Trials
(http://www.clinicaltrials.gov)
and Current Controlled Trials
(http://www.controlled-trials.com)
websites gave no indication of unpublished or current randomised controlled
trials. Our evaluation of the literature therefore relied on results from
other studies.
Effect of typical antipsychotics
Table DS1 (see data supplement to online version of this paper) summarises
the 16 quasi-experimental or observational studies which primarily used
typical antipsychotics and met our inclusion criteria
(Frithz, 1979;
Hamann & Avnstorp, 1982;
Munro, 1982;
Lyell, 1983; Ungvari,
1983,
1984; Ungvari & Vladar,
1984,
1986;
Lindskov & Baadsgaard,
1985; Bourgeois, et
al, 1986; Reilly &
Batchelor, 1986; Musalek,
et al, 1989;
Paholpak, 1990; Trabert,
1993,
1995;
Srinivasan et al,
1994; Zomer et al,
1998; Bhatia et al,
2000). The studies showed aggregate partial and full remission
rates between 60 and 100% after treatment with typical antipsychotics.
Unfortunately, the majority were not limited to primary delusional
parasitosis. Nevertheless they suggest a generally good outcome for primary
and other forms of delusional parasitosis whenever continuous antipsychotic
treatment can be established.
In primary delusional parasitosis, aggregate partial and full remission rates with pimozide ranged from 67 % (n=66; Lyell, 1983) through 89% (n=9; Munro, 1982) to 100% (n=10; Ungvari & Vladar, 1984, 1986), n=18; Ungvari, 1983, 1984). In mixed samples with primary and other forms of delusional parasitosis, aggregate partial and full remission rates with pimozide were similar and varied from 61% (n=33; Zomer et al, 1998), through 87% (n=52; Bhatia et al, 2000) to 91% (n=11; Hamann & Avnstorp, 1982). A high rate of side-effects such as sedation, extrapyramidal symptoms and depression was noted in several studies using pimozide (38%; Ungvari, 1983, 1984 and 73%; Hamann & Avnstorp, 1982).
The only two placebo-controlled trials in delusional parasitosis both used pimozide (Hamann & Avnstorp, 1982; Ungvari & Vladar, 1984, 1986). However, they are limited by a lack of randomised allocation to the treatment groups and small samples (n=10 or 11 respectively). Only Ungvari & Vladar (1984, 1986) treated patients with primary delusional parasitosis.
Studies not specific for particular antipsychotics demonstrated aggregate partial and full remission rates between 82% (n=35, not only primary delusional parasitosis, Trabert, 1993) and 89% (n=19, only primary delusional parasitosis, but some patients were treated with electroconvulsive therapy; Srinivasan et al, 1994).
The only study that investigated traditional depot antipsychotics found an aggregate response and remission rate of 93%, even in patients that could not be treated with oral medication (Frithz, 1979).
The sample consisted only of patients with primary delusional parasitosis (n=15). Another study using haloperidol reported a 100% response rate (but no full remissions) (Paholpak, 1990); nine of ten patients in this study had primary delusional parasitosis.
Across the different typical antipsychotics used, an effect of antipsychotic medication in delusional parasitosis was noted after about 3–6 weeks (Hamann & Avnstorp, 1982; Trabert, 1995). Studies came to different conclusions as to whether or not it is necessary to continue antipsychotics after successful acute therapy.
Symptoms of delusional parasitosis that were associated with major depression could be treated successfully with antidepressants (Musalek et al, 1989; Trabert, 1993; Bhatia et al, 2000).
One small study indicated that electroconvulsive therapy might be effective in patients with primary delusional parasitosis (Srinivasan et al, 1994).
A survey of British dermatologists suggested that combining psychopharmacological and dermatological treatments (local and systemic) is superior to single therapeutic approaches. Of particular note is that therapy without psychotropic medication was ineffective (Reilly & Batchelor, 1986).
We abstracted data from case series and case reports on 92 patients with primary delusional parasitosis treated with typical antipsychoticss who met our selection criteria – (see Table DS2 (data supplement to online version of this paper) (Riding & Munro, 1975; Gould & Gragg, 1976; Munro, 1978a,b, 1982; Frithz, 1979; Avnstorp et al, 1980; Ungvari, 1984; Berrios, 1985; Andrews et al, 1986; Sheppard et al, 1986; Ungvari & Vladar, 1986; May & Terpenning, 1991; Srinivasan et al, 1994; Chiu et al, 1996; Rasanen et al, 1997; Kim et al, 2003; Takahashi et al, 2003).
Table 1 shows that the majority were treated with pimozide, whereas for other typical antipsychotics only small numbers have been reported. The majority of these patients with primary delusional parasitosis were effectively treated with typical antipsychotics. Pimozide was helpful for 50 of 53 patients (94%), with 24 (45%) achieving full remission. Trifluoperazine and haloperidol appeared to be similarly effective, as did fluphenazine and flupenthixol depot.
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Effect of atypical antipsychotics
We were able to identify only 12 case reports on atypical antipsychotics
that met our selection criteria (Table
2). Although atypical antipsychotics were effective for the
majority of patients with primary delusional parasitosis only three patients
achieved full remission. All six patients for whom risperidone was prescribed,
achieved full (four) or partial (two) remission; the dosages used ranged from
1 to 8 mg per day.
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Effect of typical v. atypical antipsychotics
The five main studies of patients with primary delusional parasitosis
treated with typical antipsychotics report very heterogeneous outcomes
(Table 3), suggesting that the
studies themselves are very heterogeneous, for example in their inclusion and
exclusion criteria (selection bias) or in their definitions of partial and
full remission (measurement bias), or that there is publication bias.
Furthermore, the eight studies of patients with secondary delusional
parasitosis treated with typical antipsychotics reported heterogeneous
outcomes. This reduces the value of comparing studies reporting the use of
typical primary antipsychotics in secondary delusional parasitosis. However,
there was a large difference between the failure rate of 5% in primary
delusional parasitosis and that of at least 26% in secondary delusional
parasitosis (
2=18.2, d.f.=2, P<0.001). It follows
that studies of secondary delusional parasitosis have nothing to contribute to
the issue of the most effective treatment for primary delusional
parasitosis.
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The heterogeneity in the reported outcome of patients with primary
delusional parasitosis treated with typical antipsychotics reduces the value
of comparison with reports of atypical antipsychotics. Although the difference
is not statistically significant (
2=2.6, d.f.=2), we cannot
conclude that typical and atypical antipsychotics are equally effective
because of the innate biases already identified.
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DISCUSSION |
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Our systematic review identified no randomised controlled trials of the efficacy of typical and atypical antipsychotics in primary delusional parasitosis, probably because the disorder is rare and it is difficult to recruit patients, obtain informed consent, and achieve sufficient adherence to medication throughout a clinical trial because of their poor insight (Gould & Gragg, 1976; Munro, 1982; Ungvari & Vladar, 1986; Freudenmann & Schönfeldt-Lecuona, 2005). It is difficult to establish a good therapeutic alliance with these patients even in highly specialised settings (Trabert, 1993). Because of a lack of randomised controlled trials all our suggestions for therapy need to be interpreted cautiously. Nevertheless we are keen to provide clinicians with the current best evidence.
Use of typical antipsychotics
Our findings show that primary delusional parasitosis can be effectively
treated with typical antipsychotics. Outcome is generally good, although this
conclusion is limited by a possible publication bias. We confirm Trabert's
finding that the introduction of typical antipsychotics has substantially
improved remission rates (Trabert,
1995). Although the better studies have so far used pimozide
(Hamann & Avnstorp, 1982;
Ungvari & Vladar, 1984,
1986), the evidence for its
efficacy is weak by today's standards. The level of evidence for its use in
primary delusional parasitosis is IIa according to the criteria of the Agency
for Health Care Policy and Research
(1992), whereas other typical
antipsychotics such as haloperidol have only level III evidence. Pimozide
should not be used in patients with a high cardiac risk, together with other
substances that prolong the QTc interval
(Food and Drug Administration,
1996), or in elderly patients with delusional parasitosis.
Another important treatment in primary delusional parasitosis is the intramuscular application of traditional depot antipsychotics (Frithz, 1979), because the main problem in clinical management is to convince patients to take oral medication regularly. Injection may be more consistent with patients' (false) somatic concept of their illness and require less cooperation than oral medication. If the patient agrees to a first depot injection, the delusion may well remit at least partially and further antipsychotic treatment will be accepted. As the only study of this approach (Frithz, 1979) has only 15 patients, larger samples are needed.
Use of typical antipsychotics
Our systematic review revealed only 12 usable case reports of the use of
atypical antipsychotics in primary delusional parasitosis. These provide
limited evidence that primary delusional parasitosis can be treated
effectively with these drugs. To our knowledge, this is the first complete
collection of patients with primary delusional parasitosis treated with
atypical antipsychotics, whereas many patients with secondary forms of
delusional parasitosis have been reported in recent years (e.g.
De Leon et al, 1997;
Safer et al, 1997;
Kumbier & Kornhuber, 2002;
Freudenmann, 2003;
Le & Gonski, 2003;
Scheinfeld, 2003;
Wenning et al, 2003).
Thus the evidence for the use of atypical antipsychotics in delusional
parasitosis is even weaker than for typical antipsychotics.
Most case reports are available for risperidone, whereas we are not aware of reports on the use of clozapine, ziprasidone or aripiprazole in primary delusional parasitosis. Amisulpride might be a good alternative given that its selective D2/D3-antidopaminergic action resembles that of typical antipsychotics without the same high probability of side-effects (Freudenmann & Lepping, 2006; Lepping et al, 2006). Its lack of anticholinergic and adrenolytic effects is particularly useful in elderly patients or patients with a higher cardiovascular risk profile. Risperidone microspheres for intramuscular injection provide a potentially interesting new treatment for delusional parasitosis, as this is the only atypical antipsychotic in depot form, but this recommendation is entirely theoretical since there are no reports of the use of risperidone microspheres in delusional parasitosis at present.
Other treatment options
An alternative to these pharmacological strategies is electroconvulsive
therapy. The use of electroconvulsive therapy in a patient with delusional
parasitosis was first described by Harbauer in 1949 and has since occasionally
been reported (Baumer, 1951;
Bers & Conrad, 1954;
Hopkinson, 1970). Srinivasan
et al (1994) reported
effectiveness in primary delusional parasitosis in a small sample.
Electroconvulsive therapy might be a useful option in cooperative refractory
patients when antipsychotics are contraindicated or problematic (e.g. in the
elderly).
Synthesis
The very heterogeneous outcomes reported by the five main studies of
treating primary delusional parasitosis with typical antipsychotics (see
Table 3) suggest that the
studies themselves suffer from some or all of selection bias, measurement bias
and publication bias. Together with these flaws the paucity of evidence on
treating primary delusional parasitosis with atypical antipsychotics
undermines any comparison of typical and atypical antipsychotics. Despite
weaker evidence for the effectiveness of atypical antipsychotics in treating
delusional parasitosis in comparison with pimozide, the use of atypical
antipsychotics might improve side-effects, and thus adherence and patient
outcome.
It is important to strengthen this weak evidence in the future. We limited our selection of case series and case reports of delusional parasitosis to those including a minimum data-set for each recruited patient (age, gender, the nature and timing of diagnosis, the name and dose of medication, and the nature and timing of remission on a 3-point scale; Appendix 2).
Implications
Our systematic review generated weak evidence that antipsychotics are
effective in treating primary delusional parasitosis. However, in view of the
limited evidence, this recommendation is tentative and needs caution in
implementation. Since the introduction of atypical antipsychotics, pimozide is
no longer the treatment of choice for reasons of drug safety, even though it
has the best evidence of effectiveness in treating primary delusional
parasitosis. It is important to improve this evidence through rigorous,
ideally randomised, studies which compare typical antipsychotics and atypical
antipsychotics directly.
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APPENDICES |
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(II) Secondary forms of delusional parasitosis: secondary to another condition.
Appendix 2: Proposed minimum information required for case series and case reports of primary delusional parasitosis
Case report criteria
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Received for publication August 9, 2006. Revision received February 22, 2007. Accepted for publication February 28, 2007.
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