NADD Bulletin Volume I Number 6 Article 1

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Complications in the Diagnosis and Treatment of Depression in Persons with Down Syndrome

Caron Byrne, M.D.; Bernice Seyfort, Ph.D.

Over the last decade there has been increasing interest in mental health disorders associated with Down Syndrome (DS). Specifically, a high incidence of depression as well as early onset Alzheimer’s disease has been evident in the literature.

The purpose of this presentation is to study findings from a small group of adults with DS referred to a transdisciplinary mental health support team serving Vancouver Island and one mainland community in British Columbia. All persons included in the study have been diagnosed with depressive illness, a considerable percentage have also shown psychotic-like symptoms requiring augmentative medications. The associated incidence of early onset Alzheimer’s disease, hypothyroidism, as well as precipitating life events have all been explored. This group of individuals has been followed for an average of two years or longer and treatment outcomes monitored.

Background and Literature Review:

The nature and incidence of mental health disorders in persons with DS has been rigorously reported in the literature with some findings coming from prospective studies of fairly large groups in Britain and the United States. It is reported that persons with DS are three times more likely to experience depression than those developmentally disabled individuals without DS; with a greater number of females developing depression than males (Cooper and Collacott, l994). The average age of onset from a number of studies is approximately 30 years (Collacott, Cooper and McGrother (l992). Most commonly reported are vegetative symptoms, including sad affect, mood lability, social withdrawal, psychomotor retardation, weight loss and insomnia (Myers and Pueschel, l995). The incidence of complicating symptoms such as hallucinations and delusions varies from study to study with one reporting a presence of such symptoms in 10 of 22 cases (Myers et al, l995) while others report a markedly low incidence (Prasher and Hall, l996).

There is agreement from short term follow up studies that persons with DS who experience depression typically do not recover adaptive skills to their premorbid level, although this has been associated to some degree with age at time of onset and single versus continuous episodes of depression. Prasher et al (1996) found that although the short term prognosis for depression in adults with DS was poor, there was evidence that it was better with early age of onset. By contrast, Cooper and Collacott (l993) conclude from their research that the younger the person is when the first depressive episode occurs, the poorer the adaptive behavior scores compared with matched controls at the time of follow up. This latter study also concluded from a five-year follow up of depressed persons with DS that recurrence of depressive illness occurred in those who had their first depressive episode at an older age and those who had episodes of shorter duration. Persons with a single episode were more likely to have a longer duration than those with recurring depression. They also concluded that persons with DS whose depression becomes recurrent are less likely to have associated life events identified during the episode. The high incidence of precipitating events, even minor ones, associated with depressive episodes has also been commented on by Myers and Peuschel, (l995).

A number of studies have noted the relatively low incidence of bipolar illness in persons with DS (Craddock and Owen, l994) although there is still some dispute on this subject.

The incidence of hypothyroidism in persons with DS has been noticeably high. In one study, Prasher (l995) reported a 35% incidence. No association was however found between depression and thyroid dysfunction in this and related studies (Mortimer, l989; Collacott et al, l992; Prasher et al, l996).

Many researchers following persons with DS and depression are exploring the overlap between affective disorders and early onset Alzheimer’s disease. The incidence of the latter rises markedly past the age of fifty years in persons with DS. Symptomatology indicative of Alzheimer’s disease typically includes urinary incontinence, increased muscle tone, gait deterioration and late onset seizures. Symptoms of early dementia may be similar to depression, especially in DS individuals of higher functioning (Pary, l992). Prasher (1995) reported no association between thyroid dysfunction and dementia in his sample of persons with DS. However, depressive symptoms such as sad affect, loss of appetite, and weight loss were associated with dementia suggesting a neuropathological as well as genetic link.

Adding support to the link between depression and dementia, Meins (l995) reported an increase in depressive symptoms with age in persons with DS but not in persons with non DS related disabilities. Similarly, Burt, Loveland and Lewis (l995) have noted that depression and dementia are associated in DS but not in non DS disabled persons.

Down Syndrome cases with depression reported from a Vancouver Island Service:

The Island Mental Health Support Team serves persons with a developmental disability within a population of approximately 700,000. Since the team’s inception in l991, a total of 601 persons with a developmental disability have been referred to this service for mental health problems or very challenging behaviors. The team provides psychiatric consultation, psychology services (behavioral consultation; neuropsychological assessment) and nursing support. Clients, their caregivers, families and support persons are seen in each of the ten major communities in the geographical catchment area.

A total of 58 persons with DS were referred to this service over the past seven years. Seventeen have been diagnosed as having a depressive illness (30%). The presence of anxiety disorders, obsessive compulsive disorder and post traumatic stress disorder was noted without clear evidence of depression in a further thirteen persons (22.5%).

The mean age for the seventeen people with DS and depression was found to be 36 years (range; 16 to 54 years). Eighty two percent were women. Hypothyroidism (including two borderline cases) was diagnosed, using TSH, in 64.5 % of cases. Issues of grief and loss, either as precipitating events or delayed and presumed related were noted for 64.5% of the individuals while abuse (physical or sexual or both) was reported for 41% of persons. A preponderance of health problems was found (82.5%) which included the common syndrome-related complaints of hearing loss, cataracts and cardiac anomalies as well as other ailments including diabetes, rheumatic fever and hypertension. In brief, these individuals were generally not well, even the younger ones.

Dementia onset was confirmed for four of the seventeen individuals (23.5 %). All were over forty with one exception (age 33 years). The presence of psychotic features requiring augmentative treatment beyond antidepressants was found in seven persons in this study (41%).

Selected case studies:

Case #1

This 43 year old man has a diagnosis of DS with a moderate developmental delay, hearing loss and early cataract formation. He is not hypothyroid. He has limited verbal skills but communicates well using sign language. B. lives at home and has never been institutionalized. Prior to age 30 this man had no psychiatric history. The death of his father at about this time was accompanied by a sudden move to another province in l985. Symptoms appeared two months later which included withdrawal, poor sleep, agitation and some aggression. Haloperidol 1 mg was used (lithium was tried briefly but was discontinued). Antidepressants were not tried at this time. A slow recovery was seen and Haloperidol was continued.

Five years later B. developed hand and mouth movements and increased talkativeness. Benztropine, 2 mg was initiated which did not improve these symptoms.

When B. moved back to Vancouver Island in l994, the IMHST was called in to consult around medications. At this time a psychiatric diagnosis of specific phobia (heights) with some compulsive tendencies (repetitive hand washing) was made. No depressive symptoms were noted. Benztropine was discontinued followed by a gradual reduction (and ultimate discontinuation) of haloperidol.

Two years later there was a marked increase in repetitive hand washing, bouts of screaming, crying and complaints of being pursued by someone with a hammer. A diagnosis of depression with anxiety and obsessive compulsive symptoms was made and paroxetine 10 mg started along with Trazodone 25 mg for sleep. No antipsychotic medication was given at this time.

Four weeks later there was improvement and the paroxetine was increased to 20 mgm. Because agitation and aggression were noted two weeks hence, the lower dose (10 mg) was reestablished and 1 mg haloperidol added. Mood improved and physical aggression stopped, as did the hand washing.

After a year with no medication changes, symptoms recurred. A further .5 mg of haloperidol was added without much effect. Buspirone was started at 2.5 mg tid with gradual increases to 10 mg tid. With stabilization, the Down Syndrome Dementia Scale was carried out which showed no sign of early onset. B. is much improved with only residual signs of verbal aggression, directed mainly toward his mother. Placement with a non-family caregiver has been undertaken. Behavioral consultation for the family and counselling for B. have been offered by the servicing ministry.

Case #2

T. is a 24 year old woman with DS and a moderate developmental delay who has congenital dislocation of both hips and is being treated for hypothyroidism. She has witnessed severe domestic violence and has been emotionally and (possibly) sexually abused.

There were no psychiatric concerns until one and a half years ago when her mood and functional status began to deteriorate. Intake and dementia screening by the IMHST confirmed loss of function with strong signs of depression. After psychiatric consultation, paroxetine 10 mg was started and increased to 20 mg after two months. Thyroxine 50 mcg was started at the same time. (Because of borderline TSH results, thyroxine treatment had been delayed).

Considerable improvement in mood occurred over a couple of months however, delusional misperceptions began to appear, with obsessional preoccupation (including sexual overtones) with certain women of authority in T.’s past and present life. Visual hallucinations were also suspected. Risperidone .5 mg BID was initiated and doubled a week later. It was not clear if the unusual complications to T.’s depression were dissociative in nature and/or psychotic/delusional, however, the addition of an antipsychotic medication led to improvement.

Weekly counselling with an experienced (male) counsellor was finally established after one or two false starts with less skilled professionals. The family situation remained complex with T. first living with her mother and step father and later in a small group home. Once she had returned home, medications were cut in half and have remained at this level. T.’s mother (sadly) passed away suddenly with cancer and she has since moved to the home of a married sister. Although she continues to be reasonably stable, the layers of past abuse and the recent multiple change or living situation have had an impact on initiation and maintenance of adequate treatment.

Case #3

J. is a woman of 53 with DS, a moderate developmental delay, hearing loss, osteoarthritis and hypothyroidism. She lived at home until about ten years ago and has since lived in a non-family residence. Deterioration of mood and adaptive functioning were noted to coincide with her father’s death. Disorientation, confusion and bizarre thoughts precipitated a dementia screening about four years ago. Although there was decline in memory the main problems appeared to center around anger and depression. During an assessment by the team psychiatrist, J. disclosed that she had been sexually abused after her mother’s death. Depressive symptoms were evident including poor sleep, decreased concentration, withdrawal and reports of sadness. But more dramatic were psychotic-like symptoms including visual hallucinations and a sense of the room moving. Paranoid thinking emerged with reports of a rapist in the work place. J. was very fearful over being left alone. Past minor compulsive tendencies became stronger.

A diagnosis of major depression with psychotic features was made. Treatment was started with Moclobemide as the antidepressant with gradual increase to 225 mg bid and Loxapine 7.5 mg (divided dose) as the anti-psychotic. Physical concerns were being addressed by the client’s physician. Improvement was noted in the ensuing months, however, functional independence remained low.

Over the next year and a half, J.’s depressive symptoms were stable but anxiety and obsessive-compulsive symptoms increased. In late May of l997 a dementia screening revealed early and mid signs of Alzheimer’s disease however there was overlap with depressive symptoms. The dementia scale repeated in March of l998 showed further decline. Anxiety, fearfulness and compulsive activities remain and constant supervision has been required.

Treatment with Moclobemide continues. A brief trial with paroxetine did not prove successful. A decrease of 2.5 mg loxapine was tried in the fall of l997 but had to be returned to the initial dosage due to recurrence of psychotic symptoms.

Case #4

This 23 year old woman with a moderate developmental delay moved to a coastal village in B.C. from another province approximately a year and a half ago. At that time she was being treated for hypothyroidism; weight gain was also a problem. Shortly after she moved to a small group home in late l996, she began slapping herself and demonstrating inappropriate physical and sexual behavior in public. Her caregivers noted a very rich fantasy life verging on the delusional. Past history was difficult to come by but she had been placed on a low dose of thioridazine (30 mg per day) at age 18. This was started as angry outbursts and self-injurious behavior became evident. Her parents reported that L. had always demonstrated a rich fantasy life, however, by age 15 her fantasies took on a sexual theme, possibly fuelled by watching inappropriate videos.

At the time that L. was seen by the IMHS team, her caregivers were reporting that she was hyperactive and preoccupied with violence, especially in reference to characters from the movie ‘Terminator’. There was interaction with these ‘imaginary friends’ but it was agreed that she clearly knew they were not real. She mentioned missing former friends and was unhappy with her current day program. A diagnosis of Depression (NOS) and Anxiety (NOS) were made and treatment initiated in the form of paroxetine (started at 10 mg and increased to 20 mg).

Over the ensuing year significant improvement of mood was noted along with a decrease in self-injurious behavior, anxiety and self-talk. Work was done on providing clear boundaries and rules for displaying affection. There was also increased monitoring of movies, videos and other visual sources of violence and sexual themes.

Because of excessive weight gain, paroxetine was ultimately replaced by fluoxetine. This resulted in this young woman becoming more alert and energized. With diet changes, weight loss was achieved. Anxiety remains a problem, therefore an increase in the fluoxetine from 10 to 20 mg has been suggested.


Treating persons with DS for depressive symptoms is challenging but also very rewarding as the majority of persons ultimately improve. The art within the science approach to treatment lies in a holistic, ‘leave no stone unturned’ approach. Physical disorders are common in this population, especially hypothyroidism. Depressive symptoms may fit classic DSM IV descriptions but more frequently are complicated by anxiety, obsessive compulsive tendencies and in some cases either dementing or psychotic-like symptoms. In cases of delusions, paranoia and hallucinations it has been our experience that antidepressants should be augmented by low-dose antipsychotic medication. The duration of treatment in such cases tends to be protracted (two to three years).

When depression and dementia coexist, treating the former will usually improve quality of life. Persons with D.S. may initially present with signs of depression and then develop dementia at a later date. Regular monitoring is necessary to tease apart the two overlapping conditions and offer appropriate treatment and support.

Surprising to the authors was the high frequency of traumatic life events, some minor, others severe, found in this small group of persons with Down Syndrome. While adequate treatment with psychotropic medications is important, our team has also promoted the use of supportive counselling as part of the healing process along with education of families and caregivers.


Burt, D., Loveland, K. & Lewis, K. (1992). Depression and the onset of dementia in adults with mental retardation. American Journal on Mental Retardation, 96 (5), 502-511.

Collacott. R.A., Cooper, S.A. & McGrother, C. (l992). Differential rates of psychiatric disorders in adults with Down’s syndrome compared with other mentally handicapped adults. British Journal of Psychiatry, 161, 671-674.

Cooper, S.A., & Collacott, R.A. (1993). Prognosis of depression in Down’s syndrome. Journal of Nervous and Mental Diseases, 181, 204-205.

Cooper, S.A., & Collacott, R.A. (l994, January). Relapse of depression in people with Down’s syndrome. British Journal of Developmental Disabilities. Vol. XL, Part 1, 78. 32-37.

Craddock, N. & Owens, M. (1994). Is there an inverse relationship between Down’s syndrome and bipolar affective disorder? Literature review and genetic implications. Journal of Intellectual Disability Research, 38, 613-620.

Meins, B. (1995). Are depressive mood disturbances in adults with Down’s syndrome an early sign of dementia? Journal of Nervous and Mental Disease, 183 (10), 663-664.

Mortimer, J.A. (1989). Epidemiology of dementia: Cross-cultural comparisons. In Alzheimer’s Disease (R.G. Wortman, S. Corkin, J.H. Growdon & E. Ritter-Walker, Eds). Proceedings of the fifth meeting of the international study group on the pharmacology of memory disorders associated with aging, Zurich.

Myers, B.A. & Pueschel, S.M. (1995). Major depression in a small group of adults with Down syndrome. Research in Developmental Disabilities, 16 (4), 285-299.

Pary, R. (1992). Differential diagnosis of functional decline in Down’s syndrome. Habilitative Mental Healthcare Newsletter, 11, 37-41.

Prasher, V.P. (1995). Age-specific prevalence, thyroid dysfunction and depressive symptomatology in adults with Down syndrome and dementia. International Journal of Geriatric Psychiatry, 10, 25-31.

Prasher, V.P. & Hall, W. (1996). Short-term prognosis of depression in adults with Down’s syndrome; association with thyroid status and effects on adaptive behavior. Journal of Intellectual Disability Research, 40 (1), 32-38.

For further information contact:

Caron Byrne, MD
Island Mental Health Support Team
Box 2055
Qualicum Beach, BC, Canada V9K 1T6