H U M A N PSYCHOPHARMACOLOCY. VOL. 10, 283-288 (1995)

A Naturalistic Study in the Use of Antidepressants in Adults with Learning Disabilities and Affective Disorders S. BHAUMIK'*, R. A. COLLACOTT', D. GANDHI', C. DUGGIRALA' AND H. J . WILDGUST3 ' Frith Hospital, Groby Road, Leicester LE3 SQF, U K , ' Department of Psychiatry University of Leicester, U K , Lilly Industries, Dextra Court, Chapel Hill, Basingstoke. Hampshire, UK.

Very few studies have been undertaken looking at the use of anti-depressants in adults with learning disabilities and, more recently, with the advent of SSRIs there has not been any study comparing the use of SSRIs with tricyclic drugs in this group. A naturalistic study involving adults with learning disabilities suffering from depressive illness was undertaken in Leicestershire that included 104 treatment episodes with tricyclic/tetracyclic groups of drugs and SSRIs and issues related to efficacy, tolerability, side-effects, polypharmacy and discontinuation rates were looked at. The study, despite its limitations, establishes for the first time that depressive illness in patients with learning disabilities does respond to antidepressant treatment in the same way as that of the general population. The findings suggest that SSRIs are better tolerated and present with fewer serious side effects when compared to tricyclic/ tetracyclic groups of drugs. The efficacy of both groups of drugs was found to be very similar. This study also highlights that SSRIs are reasonably safe to use in conjunction with drugs like Lithium and Carbamazepine.

KEY woms-tricyclic antidepressants; SSRIs; learning disability; efficacy; tolerability

INTRODUCTION

The prevalence of depression in people with learn- ing disabilities cannot be stated with certainty, as different studies have reported different rates. However, most estimates are in the range of 1-5 per cent (Wright, 1982). These difficulties are compounded by the lack of valid and reliable diagnostic criteria especially for people with severe/profound learning disabilities and those with limited/compromised communication skills.

It is largely acknowledged that depression is under-recognized in this population, as suggested by the excessive use of neuroleptics and infrequent use of antidepressants (Chandler et al., 1988).

Antidepressant use in adults with learning disabilities has been almost exclusively limited to tricyclic antidepressant drugs. More recently, with the advent of SSRIs, the picture has started to change. There have been virtually no systemic placebo controlled drug trials of the treatment of depression in people with learning disabilities and research on antidepressant drug use is largely confined to various case reports. The picture is further complicated by co-existing disabilities,

*Author to whom correspondence should be addressed.

CCC 0885-6222~SS/O40283-06 Q 1995 by John Wiley & Sons, Ltd.

including epilepsy and use of polypharmacy, which tend to exclude the patients from most of the clinical trials.

There is a shortfall in the literature on the use of SSRIs in this group of patients. The few studies include that of Howland (1992) who demonstrated the use of fluoxetine in the treatment of depression in retarded people. He conducted an open trial of fluoxetine in six depressed mentally retarded adults, of whom five responded well to fluoxetine and one responded partially. None of the patients experienced any major side-effects. Sovner et al. in 1993 found fluoxetine to be useful in two patients with self-injurious behaviour and depressive symptoms.

Of all the studies carried out in the general population, Song et al. (1993) carried out a meta- analysis of 63 randomized controlled trials comparing the efficacy and acceptability of SSRIs with those of tricyclic antidepressants Their findings suggested that there was no statistical or clinically significant difference in acceptability and efficacy between the two groups in patients with major depression. Therefore they concluded that the use of SSRIs as the first line of treatment of depressive illness may greatly increase costs with questionable benefit. However, Montgomery et a!.

284 S . B H A U M I K E T A L .

SSRI group

(1994) carried out meta-analysis of 42 published randomized control trials comparing SSRIs with the tricyclic antidepressants that included dis- continuation rates for side-effects and lack of efficacy by treatment group. Their findings suggested that significantly fewer patients receiv- ing SSRIs discontinued treatment because of side- effects (14.9 per cent) compared to those receiving TCAs (I9 per cent). There was no difference in the discontinuation rates for lack of efficacy between the two groups. Hence the conclusion was that SSRIs should be used as first line of treatment for depression since there were similar levels of efficacy but more discontinuations with the TCAs due to side-effects.

This naturalistic study aims to look at the use of antidepressants including that of tricyclics, tetra- cyclics and SSRIs in people with learning disabilities suffering from depressive illness and comments on their reported clinical efficacy and side-effect profile.

TCA/tetracyclic group

METHODS A retrospective case note analysis was carried out involving all the adults (aged 18 years and over) who have been in contact with the services provided by the Department of Psychiatry of Mental Handicap in Leicester froin a defined geographical area involving Leicester City carry- ing a total population of around 300 000 in the last three years.

The case notes of all patients who have been in contact with the Department were examined and only the patients with ICD 9 diagnosis of depression and who were not on any antidepres- sant treatment prior to the study period were included. The case notes included details of chronological history, symptomatology, mental state examination, ICD 9 diagnosis and manage- ment plans. The case notes of those patients diagnosed as suffering from depression were

Table 1. The class of antidepressant chosen for each episode of treatment and the association with gender

Males Females Total treatment episodes

studied in detail and the following information was extracted: age, sex, secondary handicaps including epilepsy, degree of learning disability, treatment received, reported side-effects, duration of treatment and treatment outcome. The treat- ment outcome was measured by using clinical global improvement scale. Concurrent use of other medications was also noted.

RESULTS

The total number of case notes studied was 71, including 26 males and 45 females. The excess of females over males was statistically significant

The age ranges for males and females including mean age were estimated and were found to be similar. The mean age for males was found to be 38.3 years with an age range of 21-80 years. For females the mean age was noted to be 40.6 years with an age range of 18-72 years.

The prevalence of active epilepsy between the male and female groups was estimated and was found to be similar. The total prevalence of active epilepsy was noted to be around 20 per cent (n = 14) and its distribution in the male and female groups was found to be around 23 per cent (n = 6) and 18 per cent ( n = 8) respectively.

Both male and female groups were found to be predominantly mildly learning disabled and, over- all, the degree of disability did not appear to differ much between the two groups. In the male group 69 per cent belonged to the mild category, 26 per cent belonged to moderate category, 8 per cent to severe category and none (0 per cent) in profound category. The distribution in the female group showed 56 per cent belonging to mild category, 36 per cent to moderate category, 8 per cent to severe category and none (0 per cent) in the profound category. The overall prevalence of the degree of learning disabilities was 60 per cent mild category, 31 per cent moderate category, 9 per cent severe category and none (0 per cent) in the profound category.

Case notes analysis revealed altogether 104 treatment episodes (Table 1). Distribution of antidepressant drugs and average dosage in the two groups are illustrated below (Table 2). The difference between the two groups in terms of side- effects was noted (Table 3). The distribution of the episodes of side-effects between the two groups is illustrated in Table 4. The discontinuation rates between the two groups due to side-effects and

(p < 0425).

LEARNING DlSABlLITlES A N D ANTIDEPRESSANT USE 285

TCA/tetracyclic group SSRI group

Drugs

Prothiaden Lofeprarnine Ami tryptilene Imipramine Others inc.

Mianserin Trazadone Doxepin

Side-effects

No. of treatment episodes inc. %

13 (31%) 10 (24%) 7 (17%) 7 (17%)

1 2 2

5 (11%)

No side-effects Total

Average dose

150 mg 210 rng 150 rng 150 rng

50 rng 150 mg 150 rng

- SSRI '9 (14.5%)

Total 27 (26%) TCA/tetracyclic 18 (43%)

No. of treatment Average Drugs episodes inc. % dose

Fluoxetine 34 (55'/0) 20 mg Paroxetine 22 (35%) 30 rng

Others inc. 6 (IOYo) Sertraline 4 100 mg Fluvoxarnine 2 200 mg

53 (85.5%) 62 (1 00%)

7'7 (74%) 104 (100%) 24 (57%) 42 (100%)

X' = 10.47. dJ"= I . /~<0.005.

lack of efficacy is shown in Table 5. Sixty-nine per cent of patients in the SSRI group and 68 per cent of patients in the TCA group were receiving other medications (Table 6). Serum lithium levels before and during treatment with SSRIs and TCAs were recorded (Table 7).

The clinical efficacy in the two groups were estimated by using CGI scale and the mean CGI scores were compared. The mean CGI score for the SSRI group was 2.09 (mean score) whilst the mean CGI score of TCA/tetracyclic group was noted to be 1.96 (mean score).

Table 4. Episodes of side-effects

1 SSRI group 1 TCA group Agitation Diarrhoea Drowsiness Dry Mouth Epileptic seizures H ypornania/mania insomnia Leucopaenia Nausea Obesity Postural hypotension

Total episodes

4 1 0 0 0

9

The mean CGI scores for patients treated with fluoxetine and paroxetine were noted to be 2.06 and 2.08 respectively. (CGI scale: 1 = very much improved; 2 = much improved; 3 = minimally improved; 4 = no change; 5 = minimally worse; 6 = much worse; 7 = very much worse).

DISCUSS ION The problem in carrying out a placebo-controlled randomized clinical drug trial in the field of learn- ing disabilities is well known and includes many

Table 5. Discontinuation rates between the two groups

(n = 62) (n = 42)

Due to side-effects 1 1 (26%) Due to lack of efficacy 1 ::::;; 1 4 (9.5%)

Total I 10 (16%) 1 15 (36%)

Table 6. Distribution of polypharmacy by group ~~

Neuroleptics 54% Lithium 15% 14% Anticonvulsants 17%

286 S . BHAUMIK ET AL.

Table 7. Serum lithium levels following treatment with SSRIs and TCAs ~~

Pre-treatment with During treatment Pre-treatment During treatment SSRI with SSRI with TCA with TCA

15% ( n = 9) 15% (n = 9) 14% ( n = 6) 14% (n = 6)

Serum lithium levels 0.42 0.56 0.61 0 46 0.56 0.57 1.27 0.94 0.56 0.54 0.65 0.67 0.75 0.75 0.56 0 60 0.88 0.77 0.67 0.75 0.4 1 0.55 0.30 0.38 0.22 0.37 0.85 0.85 0.6 1 0.58

Average serum lithium values

0.58 0.61 0.67 0.63

ethical and consent issues. Also taking into account the extent of polypharmacy and co-existing physical conditions including epilepsy in the learning disabled population, if a clinical trial is to be undertaken the majority of patients would be excluded from it and, therefore, conclusions drawn from such a trial will be highly questionable. Similar problems are encountered in the elderly general population, mainly because of co-existing physical disabilities and the extent of polyphar- macy. Our study has the strength of being naturalistic and therefore, reflected what happened in real clinical practice as there were no exclusion criteria. However, it has its limitations of being a retrospective case note analysis and therefore caution should be exercised in drawing definitive conclusions. The problems of retrospective studies are well known and include that of individual variation in the quality of record keeping, recording of critical events, frequency of contacts etc. Many of these problems can be alleviated if the record keeping is detailed and is in accordance with a clearly laid out management plan which, fortunately, has been the case in our study.

The results show that the depressive illness amongst adults with learning disabilities has the same pattern as the general population in terms of age and sex distribution. The prevalence of epilepsy in our study group has been found to be similar to that of the learning disabled population in general (Corbett et a[., 1975).

Considering the degree of learning disabilities between the two groups of patients the majority were found to be only mildly learning disabled, highlighting the fact that perhaps the standard diagnostic criteria of depression are applicable for

this group of people. The hitherto lack of depression amongst the severe and profound group of learning disabled people highlights the usual problems of diagnosing depression in this group because of the language and intellectual impairment. Thus clinical evaluation of depression and treatment response might be inadequate, leading to greater reliance upon non-specific global assessments.

The average dosage of antidepressant drugs used in the treatment episodes (Tables 1 and 2) suggest that the clinicians were able to use antidepressant drugs in full therapeutic dosage in contrast to. the popular belief that the learning disabled population can tolerate only a smaller dosage of psychotropic medication.

So far as side-effects are concerned, the overall prevalence was noted to be 26 per cent (n = 27) including both the groups. It is also important to note that about 68-69 per cent of patients belonging to both SSRI and TCA groups were receiving other medications at the same time. The difference in side-effects reported by the SSRI and the TCA/tetracyclic groups was noted to be statistically highly significant (Table 3). Only 14.5 per cent of the patients experienced side- effects in the SSRI group when compared to the tetracyclic/tricyclic group where 43 per cent of the patients experienced some form of side-effect. The tetracyclic/tricyclic drugs caused significantly more and serious side-effects (Table 4) including that of postural hypotension, worsening of seizures and unacceptable degree of drowsiness.

The patients receiving tetracyclic/tricyclic drugs also suffered from many anticholerginic drug side- effects which may adversely affect learning in

LEARNING DISABILITIES A N D ANTIDEPRESSANT USE 287

persons with mental retardation (Werry, 1980). In addition, the contribution of brain damage (which occurs in many cases of mental retardation) and anticholergenic drugs is an important predisposing factor for delirium (Lipowski, 1987). Antidepres- sant drug choice in this clinical population should therefore be made very carefully and drugs with minimum anticholinergic effects may be preferred. Secondly reduced central nervous system serotonin is known to be associated with aggressive and impulsive behaviour (Coccaro, 1989). Aggressive behaviour can itself be a manifestation of emotional disturbance in mental retardation and it is the most common reason for prescribing psychotropic drugs in patients (Aman, 1987). Drugs that enhance serotonin might be especially beneficial in this population, or at least in a sub- group characterized by reduced serotonin. Aneco- dotal reports demonstrating the positive effects of SSRIs in aggressive mentally retarded patients support this hypothesis (O’Neil et al., 1986; Gaultieri, 1989). Comparing the efficacy of antidepressants having different potentials, e.g. fluoxetine versus paroxetine, in a study of mentally retarded patients with depression and aggression might clarify this issue further.

Table 5 shows that discontinuation due to side- effects is considerably higher in the tricyclic tetracyclic group (26 per cent) compared to the SSRI group (9-6 per cent) suggesting a potential advantage of the use of SSRIs in adults with learning disabilities suffering from depressive illness. The overall discontinuation rate in the SSRI group has been found to be about 16 per cent, similar to studies carried out in the general population.

The relative lack of toxicity despite the high extent of polypharrnacy (Table 6) suggests that SSRIs are safe to use in combination with drugs like lithium and carbamazepine, provided basic precautions are maintained and blood levels are monitored on a regular basis. The average rise of serum lithium value with the concurrent use of SSRIs was found to be to the extent of 0.03 mmol/l only (Table 7) which is reassuring. This finding appears to be similar to that of the other studies (Hopwood et af., 1993).

Finally, the clinical efficacy of both SSRIs and tricyclics/tetracyclics appears to be very similar using CGI scale, but there is a significant difference insofar as side-effects are concerned. SSRIs appear to be safer, better tolerated and relatively free from serious side-effects.

The findings of our study support the meta- analysis carried out by Montgomery et af. (1994) which suggested that significantly fewer patients receiving SSRIs discontinued treatment because of side-effects when compared to those receiving TCAs. This finding is, however, in contradiction to the claim by Song et al. (1993) that the routine use of SSRIs as the first line of treatment of depressive illness may greatly increase costs with questionable benefit.

The assessment of risks and benefits of treat- ment must include the patient’s quality of life. Discontinuation rate due to the side-effects of antidepressant drugs, suggest that SSRIs should be used as the first line of drug choice in the treatment of depression. They demonstrate a significant advantage in terms of tolerability and lack of serious side-effects when compared to tricyclics/ tetracyclics. The efficacy of both groups of drugs is similar.

CONCLUSION

This study, despite its limitations, establishes for the first time that depressive illness in patients with learning disabilities does respond to antidepressant treatment in the same way as that of the general population. This study strongly suggests that SSRIs should be the first line of drug in the treatment of depression in learning disabilities because of their better tolerability, lower disconti- nuation rates due to side-effects whilst their efficacy is similar to that of tricyclics.

Finally, bearing in mind the difficulties of conducting placebo-controlled randomized drug trial in the field of learning disabilities, we suggest further research is required in this area through naturalistic prospective studies. They are likely to generate valuable data which will aid in the clinical management of depressed patients.

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