Depressive illness in the presence of medical illness is common and the relationship between them is complex. Often the medical illness can cause the depression. However, in some illnesses depression may be the primary presentation. Depression in medically ill patients may be difficult to diagnose. The assessment of both conditions and the interaction between them is critical in managing these patients. A review of the medical disorder and the patient's medications is important. Psychotherapy may be sufficient to treat mild depression. However, for more severe depression antidepressants may be required, or referral to a psychiatrist. The patient and their family are likely to need long-term support.



Depressive illness in patients with medical illness is common and has extensive implications for the patient and their family, and the treating doctor. The co-occurrence of these disorders results in amplification of suffering, increased morbidity and mortality, prolonged hospital stays and increased utilisation of healthcare services.

Unfortunately, the diagnosis of depression in the presence of medical illness is frequently missed, often resulting in unnecessary investigations and procedures, increased disability and increased costs to the community. The main issues in dealing with depression in this context are making an accurate diagnosis, teasing out the complexity of the interaction between the depression and the medical illness and establishing an appropriate management plan that addresses both problems and the interactions between them.


The extent of the problem

Rates of depression vary with the nature of the medical disorder. The most common associations are found in neurological, cardiovascular, endocrine and oncological illnesses, but can occur in almost any disorder. It has been reported that around 30% of patients attending a neurological clinic had significant symptoms of depressive illness and in up to 72% of these patients the depression was unrecognised by the physician.1The prevalence of depression following acute ischaemic heart disease may be as high as 30% and the risk persists for 12 months following myocardial infarction. After stroke the prevalence of depression may be as high as 31% at three months.2In cancer patients after the diagnosis, the risk of depression is as high as 55%.

Comorbid depression has been suggested to increase the death rate of the underlying illness by as much as 4.3 times regardless of whether the patient was previously healthy or not.3In haemodialysis patients, depression predicted mortality after adjusting for age, gender, race, medical comorbidity and several biochemical markers.4Depression was also found to be a significant predictor of cardiac mortality in patients with recent myocardial infarction.5There is some evidence that treating depression in cardiac patients following myocardial infarction or those with unstable angina may reduce subsequent cardiac events.6This may be due to antiplatelet aggregation effects that have so far been documented following treatment with the selective serotonin reuptake inhibitors sertraline, paroxetine and escitalopram.7,8

Compared with non-depressed patients, those with comorbid depression have increased mortality, prolonged length of hospital stay and greater number of days in hospital on follow-up.9


The relationship between depression and medical illness

The association between depression and medical disorders is complex. The depressive illness may be a consequence of the medical illness or may be a primary issue. For example, depressive symptoms frequently present in Parkinson's disease, stroke, space-occupying lesions of the central nervous system, and endocrinopathies such as Cushing's syndrome and thyroid disorders. Depressive symptoms may precede the onset of some disorders including hypothyroidism, ischaemic heart disease and stroke and may even contribute to their causation through alterations in platelet adhesion and immunological changes.

The exact biological mechanisms by which these illnesses may cause depression are yet to be determined. However, reduced dopamine availability has been suggested in illnesses such as Parkinson's disease. Destruction of central nervous system pathways have been implicated in depression, especially in patients with central nervous system lesions. Hormonal modulation of central monoamine receptors may explain some depression in the endocrinopathies.

Finally, the association between depression and medical illness may be explained by factors that can lead to both disorders. For example, stress and substance abuse may lead to the development of stress-related and substance-related medical disorders and depression.


Making the diagnosis

A careful history of the onset, course and severity of the depressive symptoms is required. This may help tease out whether the depression is primary or secondary and also the relationship between the severity of physical symptoms of illness and degree of depression. Risk factors, such as those for suicidality, should always be assessed.

Appropriate investigations (for example thyroid, blood, liver and renal function screen and neuroimaging) are needed to exclude an organic cause of depression and to assess the status of the medical illness. Specific metabolic investigations may be needed depending on the medical disorder, for example calcium concentrations in patients with metastatic cancer.

Depression in medically ill patients may be overlooked by the busy medical practitioner. This is partly due to the 'understandability' of the depressive symptoms and the dominance of the physical presentation of the disorder. However, the constellation of the depressive symptoms may also be difficult to recognise in the presence of a major medical disorder.

Depressive symptoms can be grouped into biological (e.g. sleep, appetite), psychological (e.g. preoccupations with guilt, failure) and social (e.g. withdrawal, loss of role). Psychologically-based symptoms such as dissatisfaction, a sense of failure, feeling the illness was punishment, suicidal thoughts, crying and loss of social interest in family and friends are the most discriminating symptoms of depression in medically ill patients.10When sleep disturbance is unexplained by the medical disorder and is accompanied by ruminatory thoughts of guilt, failure and hopelessness, it may also help in the diagnosis. This is also true for unexplained weight loss.

The diagnosis may be complicated by substance abuse. Depression and substance abuse may frequently coexist and contribute to the expression of either disorder. Alcohol, cannabis and amphetamines have been directly implicated in the cause of depression.


Managing the medical illness

A review of the medical disorder is important. This may include minimising unnecessary medication and maximising the treatment of the medical condition. Rehabilitation approaches to chronic problems such as pain, neurological disorders, arthritis and some cancers should be considered. It can be helpful to give advice regarding a healthy lifestyle including diet, sleeping habits, substance misuse and regular exercise within the constraints of the medical problem. Improvements in the individual's functioning can have considerable benefit in terms of self-esteem and mood.


Managing the depression

Although optimising the management of the medical illness may improve the patient's mood, the depression may still require specific management. This includes psychotherapeutic techniques and antidepressant medications.

When the symptoms are mild to moderate, psychotherapy is indicated. Cognitive behaviour therapy is often well suited for these patients. Standard elements may include challenging negative thinking and catastrophisation, relaxation techniques, behavioural scheduling which may include regular exercise and socialisation and problem solving techniques.

When the depressive disorder is moderate to severe, medications may be required. Older tricyclic antidepressants and monoamine oxidase inhibitors should be avoided as first-line drugs since they may interact and worsen the underlying medical disorder due to anticholinergic, anti-adrenergic and cardiac effects. As many patients will be on multiple medications for their underlying physical disorder, care should be taken to avoid drug interactions. In order to counter altered metabolism and minimise adverse effects, medications should be started at low doses and adjusted slowly.

When the depression is severe with suicidal ideation or the interaction with the medical disorder is complex, referral to a psychiatrist may be indicated. Electroconvulsive therapy (ECT) can be used when the depression is severe. However, caution is required and ECT is contraindicated in patients with uncontrolled hypertension or raised intracranial pressure.

In all cases, frequent liaison with other professionals involved with the management of the patient is essential. In some disorders such as chronic pain, the interactions between illness and depression are so complex the patient is best managed in a multidisciplinary rehabilitation program where physician, psychiatrists, psychologists and physical therapists meet regularly and address the issues in a co-ordinated approach. Changes to the Medicare Benefits Schedule may make it easier for patients to access these services.


Patient support

As with all therapeutic interactions, and in particular when they are complex and likely to be prolonged as in the case of comorbid depression with medical illness, a good rapport with the patient and their family is essential. This will begin with education of the patient and their family about both the medical disorder and the depressive disorder. Often there are negative judgments from family members who may be critical of the patient for not trying or using the symptoms to avoid the usual responsibilities of their role. On the other hand, some families may perpetuate disability and not encourage the patient to maximise their capacity. The patient and their family are likely to need a prolonged period of support which may be best supplied with regular appointments.


Self-test questions

The following statements are either true or false.

1. Dothiepin is the first treatment of choice for patients with comorbid depression and medical illness.
2. Unexplained weight loss and sleep disturbance should not be considered signs of depression in medically ill patients.

Answers to self-help questions

1. False
2. False


  1. Bridges KW, Goldberg DP. Psychiatric illness in inpatients with neurological disorders: patients' views on discussion of emotional problems with neurologists. BMJ 1984;289:656-8.
  2. Astrom M, Adolfsson R, Apslund K. Major depression in stroke patients. Stroke 1993;24:976-82.
  3. Bruce ML, Leaf PJ. Psychiatric disorders and 15-month mortality in a community sample of older adults. Am J Pub Health 1989;79:727-30.
  4. Drayer RA, Piraino B, Reynolds CF, Houck PR, Mazumdar S, Bernardini J, et al. Characteristics of depression in hemodialysis patients: symptoms, quality of life and mortality risk. Gen Hosp Psychiatry 2006;28:306-12.
  5. Frasure-Smith N, Lesperance F, Talajic M. Depression and 18-month prognosis after myocardial infarction. Circulation 1995;91:999-1005.
  6. Glassman AH, O'Connor CM, Califf RM, Swedberg K, Schwartz P, Bigger JT, et al. Sertraline treatment of major depression in patients with acute MI or unstable angina. JAMA 2002;288:701-9.
  7. Malinin AI, Ong S, Makarov LM, Petukhova EY, Serebruany VL. Platelet inhibition beyond conventional antiplatelet agents: expanding role of angiotensin receptor blockers, statins and selective serotonin reuptake inhibitors. Int J Clin Pract 2006;60:993-1002.
  8. Atar D, Malinin A, Takserman A, Pokov A, van Zyl L, Tanguay JF, et al. Escitalopram, but not its major metabolites, exhibits antiplatelet activity in humans. J Clin Psychopharmacol 2006;26:172-7.
  9. Koenig HG, Shelp F, Goli V, Cohen HJ, Blazer DG. Survival and health care utilization in elderly medical inpatients with major depression. J Am Geriatr Soc 1989;37:599-606.
  10. Clarke DC, Cavanaugh SV, Gibbons RD. The core symptoms of depression in medical and psychiatric patients. J Nerv Ment Dis 1983;171:705-13.

James S Olver

Senior Lecturer, Department of Psychiatry, University of Melbourne, Austin Hospital, Austin Health, Melbourne

Graham D Burrows

Medical Director, Department of Psychiatry, University of Melbourne, Austin Hospital, Austin Health, Melbourne