The course of tardive dystonia in Afro Caribbean patients, a population-based study: The Curacao Extrapyramidal Syndromes Study: VII

1. Introduction 

Tardive dystonia (TDt) is a severe side effect of antipsychotic treatment. The dystonic features affect different areas, most frequently resulting in blepharospasm, torticollis and hand dystonia. Although TDt has been identified as a distinct subtype of tardive dyskinesia since 1982, it is surprising that there have been no population-based studies on the course of TDt (Burke et al., 1982; Burke, 1992). Data about the course of TDt come from case series based on selectively referred populations, in which referral bias has probably influenced the results (Burke et al., 1982, Kang et al., 1988, Wojcik et al., 1991, Kiriakakis et al., 1998).

Since the introduction of Second Generation Antipsychotics (SGAs) it has been assumed by some clinicians that tardive syndromes are no longer clinical relevant. However, although the incidence of tardive syndromes with SGAs may be lower than with First Generation Antipsychotics (FGAs), the incidence is not nil (Correll et al., 2004). Furthermore, many patients continue taking FGAs alone or in combination with SGAs, e.g. patients with depot antipsychotics or who are intolerant to the side effects of SGAs (Ganguly et al., 1998, Broekema et al., 2007, Lieberman et al., 2005). In addition, the non-commercially sponsored CATIE and CUtLASS trials suggest that SGAs may not be superior over FGAs with regard to effectiveness, tolerability and quality of life. However, these studies have serious limitations regarding dosage schedules, drop out rate and patient selection which affect the validity of the conclusions (Lieberman et al., 2005, Jones et al., 2006). The high incidence of weight gain and the metabolic syndrome associated with some of the second-generation antipsychotics question the advantages claimed for SGAs (Kane, 2006). Furthermore, in those countries with limited budget for psychiatric healthcare FGAs are the standard antipsychotics (Kasper et al., 2006, Patterson et al., 2005). Therefore, FGAs still play a role in the treatment of psychotic disorders and, consequently, tardive syndromes remain an important clinical issue.

Previously, cross-sectional data pertaining to this population were published (van Harten et al., 1996a, van Harten et al., 1998). As this population now has been followed for nine years, follow-up data were used in the current report to examine the expression and the course of TDt.

2. Subjects and methods 

The methods have been described in detail previously (van Harten et al., 2006) and are repeated briefly.

3. Results 

Included in the study were 194 patients with a mean age of 53.1 yrs (SD 16.7), male female ratio of 2.7 and the following diagnostic distribution (a patient can have multiple diagnosis): schizophrenia 77.3%, affective disorder 5.2%, dementia 8.2%. mental retardation 4.6%, cocaine abuse 13.9% and other diagnosis 24.7%.

Of the 194 patients included, 26 had TDt at baseline (18 males, mean age 45.9, SD 14.0 and 8 females, mean age 70.0, SD 15.2). Of the 168 patients without TDt at baseline, 42% participated at all six follow-up assessments and 14%, 6%, 5%, 8%, 10% and 16% had 5, 4, 3, 2, 1 and 0 follow-up assessments, respectively. Of the 26 prevalent TDt cases at baseline, 58% participated at all six follow-up assessments and 8%, 8%, 4%, 0%, 19%, and 4% had respectively 5, 4, 3, 2, 1 and 0 follow-up assessments. Further data on attrition are presented in Table 1.

Table 1. Title: The severity of tardive dystonia based on the score on the Fahn–Marsden rating scale during the nine-year follow-up (one baseline and six follow-up assessments)a

	Case	Age	Sex	T0		T1		T2		T3		T4		T5		T6
				FMS	AP	FMS	AP	FMS	AP	FMS	AP	FMS	AP	FMS	AP	FMS	AP	Outcomeb
	1	81	F	1.5	FGA	0	FGA											Remission
	2	34	M	2	FGA	0	FGA	0	FGA	0	FGA	0	FGA	0	FGA	0	FGA	Remission
	3	54	M	4	Risp	8	FGA	0	FGA	0	FGA	4	FGA	0	FGA	10	FGA	Intermittent
	4	74	F	4	FGA	9	FGA	0	FGA	0	FGA	0	FGA	0	FGA	0	FGA	Remission
	5	79	F	4.5	FGA	0	FGA	30	FGA	1.5	FGA							Intermittent
	6	54	M	6	No AP	4	No AP	0	FGA	0	FGA					0	FGA	Remission
	7	67	M	6	No AP	8	No AP	16	No AP	8	No AP	8	No AP	6	No AP	0	FGA	Remission
	8	59	M	6.5	FGA	8	FGA	0	FGA	0	FGA	0	FGA	4	FGA	0	FGA	Remission
	9	91	F	8	FGA	0	FGA											Remission
	10	61	M	8	FGA	12	FGA	0	FGA	12	FGA	0	FGA	0	No AP	0	No AP	Remission
	11	38	M	10	FGA											0	Ola	Remission
	12	62	M	10	FGA	24	No AP	10	FGA	0	FGA	0	FGA			0	FGA	Remission
	13	39	M	12	FGA	9	FGA	8	FGA	16	FGA	16	FGA	0	FGA	0	FGA	Remission
	14	42	M	12	FGA	24.5	FGA	14	FGA	29	FGA	10	FGA	4	FGA	10	FGA	Persistent
	15	60	F	12.5	No AP	0	No AP	0	No AP	0	No AP	0	No AP	0	No AP	0	No AP	Remission
	16	67	M	14	FGA	13	FGA	0	FGA	0	FGA			0	FGA	0	FGA	Remission
	17	37	M	14	FGA	19	FGA	37	FGA	37	FGA	28	FGA	0	FGA	10	Ola	Intermittent
	18⁎	36	M	16	FGA	10	CLZ	4	CLZ	0	CLZ	8	CLZ	0	CLZ	0	CLZ	Remission
	19⁎	31	M	19	FGA	0	CLZ	0	CLZ	0	CLZ	0	CLZ	0	CLZ	9	CLZ	Intermittent
	20⁎	25	M	20	FGA	0	CLZ											Remission
	21	64	F	21	FGA													No follow up
	22⁎	55	M	26	FGA	10	CLZ	16	CLZ	14	CLZ	11	CLZ	12	CLZ	14	CLZ	Persistent
	23	71	F	28	FGA	26	FGA											Persistent
	24⁎	42	M	37	FGA	28	CLZ	36	CLZ	31	FGA	33	FGA					Persistent
	25⁎	24	M	53	FGA	2	CLZ	0	CLZ	4	CLZ	0	CLZ	3	CLZ	0	CLZ	Remission
	26⁎	41	F	61	No AP	53	CLZ	55	FGA	49	FGA	48	FGA	40	FGA	33	Ola	Persistent

FMS = Score on the Fahn–Marsden Rating Scale; AP = Antipsychotic; No AP = No Antipsychotic; FGA = First Generation Antipsychotic; Ola = olanzapine; Risp = Risperidone; CLZ = Clozapine.

a Baseline was in 1992, post-baseline follow-up assessments were in 1993, 1994, 1996, 1997, 1998 and 2001. b For definition: remission/intermittent/persistent (see text).

The characteristics of the patients without TDt at baseline were published previously (van Harten et al., 1996a).

4. Discussion 

This population-based study showed that the course of TDt in patients with TDt at baseline is relatively favorable compared to the course described in previous studies that were based on selected populations mainly from specialized movement disorder clinics. The remission rate in the current study of 64% in prevalent and even 80% in incident cases is in contrast with the 10 to 20% remission rate reported in previous studies (Burke et al., 1982, Wojcik et al., 1991, Kiriakakis et al., 1998, Kang et al., 1986). On the other hand, if a patient had severe dystonia, the remission rate was low. Of the 5 prevalent TDt patients with the most severe ratings, only one recovered. Therefore, severity of TDt seems to be a strong predictor for persistence. This is in line with previous studies showing low remission rates in patients with severe TDt (Burke et al., 1982, Wojcik et al., 1991, Kiriakakis et al., 1998, Kang et al., 1986). Although severe TDt was often persistent, switching to clozapine was effective in 3 of the 7 patients. This has also been reported in several case series (Kiriakakis et al., 1998, van Harten et al., 1996b, van Harten and Kahn, 1999).

Only one population-based study reported on the course of seven patients with moderate to severe TDt and only one patient recovered during four years of follow-up (Yassa et al., 1986).

The body areas most affected were hands, eyes (blepharospasm), neck and mouth. Also several case series showed that the craniocervical region and the upper limbs were among the most frequently involved (Burke et al., 1982, Wojcik et al., 1991, Kiriakakis et al., 1998, Kang et al., 1986).

This study has several strengths. First, the Netherlands Antilles are ideally suited for epidemiological research because the catchment area, being an island, is well defined and the study included all psychiatric inpatients. Furthermore, patients can easily be tracked after discharge from hospital, resulting in low attrition rates. Moreover, one baseline and six follow-up assessments over a nine-year follow-up period will give a more accurate estimate of the course of TDt than studies with only a few assessments or a relatively short duration. The accuracy of the estimates was further enhanced because the same two investigators carried out all follow-up assessments simultaneously, ensuring continuing reliability and comparability of assessments over time.

5. Conclusion 

The course of TDt depends of the severity of TDt; mild cases often recover whereas severe cases tend to persist. If severe cases do not respond on pharmacological treatment, deep brain stimulation can be considered (Broggi et al., 2006). It is important that clinicians remain on the lookout for emerging cases regardless of what medication(s) the patient is receiving. When early signs of TDt are detected several interventions can be considered, one possibility being a switch to another agent with a potentially lower risk on TDt such as clozapine (van Harten 1996b).

Role of funding source 

This research was supported by a grant from the Netherlands Antilles Foundation for Clinical Higher Education (NASKHO). The NASKHO is a leading supplier of medical training, post-graduate courses and medical conferences. Established in 1967, NASKHO has provided superior service to our stakeholders and have assisted them in achieving their goals. The foundation is financially supported by the government.

Contributors 

Peter N van Harten and Glenn Matroos designed the study. Peter N van Harten wrote the protocol and managed the literature searches. Peter N. van Harten and Jim van Os undertook the statistical analysis. Peter N. van Harten, Glenn Matroos and Jim van Os contributed to all the drafts of the manuscript.

All authors contributed to and have approved the final manuscript.

Conflict of interest 

Peter N. van Harten has been speaker for Janssen Cilag BV, Eli Lilly, Bristol-Myer Squibb, and Pfizer.

Jim van Os is a grant holder, speaker or advisory board member with Lilly, BMS, Lundbeck, Organon, Janssen-Cilag, GSK, Otsuka and AstraZeneca.