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A 35-year-old man with background history of cardiac failure and renal disease presented to the emergency department with dysarthria, left-sided facial weakness and left upper-limb weakness. CT brain demonstrated right anterior cerebral infarct. He was thrombolysed and had some residual deficits. He was enrolled in a rehab programme with input from a multidisciplinary team.
He was referred to the liaison mental health team for assessment of mood. The patient described an 18-month history of low mood following a previous admission to hospital for cardiac related issues. He denied suicidal thought but described having anticipatory anxiety during this period. He found it difficult to get back to work during this time and felt that he was a burden due to his illness. He reported avoiding contact with friends and work colleagues, as he didn’t wish to be seen as a ‘failure’ due to his inability to work. He was noted to be a poor attender at outpatient clinics and had engaged poorly with rehab programmes. Collateral suggested he had been irritable during this time and had become withdrawn. Pre-morbidly, he was described as ‘bright’, ‘bubbly, and ‘outgoing’.
The patient reported that his mood had improved in the months prior to his stroke. His partner was pregnant, and he was in the process of applying for a college course. While he felt his mood was much improved, he had ongoing worries about his physical health, and whether he would be in a position to support a child given his illness. He also worried about his own mortality and potentially shortened life expectancy.
Following initial assessment, it was felt that patient had obsessional anxiety, with avoidance pattern of thinking relating to his illness. He was followed in the liaison mental health clinic and engaged in supportive therapy.
Two months after his initial assessment, he was seen in clinic, he presented with poor sleep, increased thinking about his physical illnesses and likely impact on his life in the context of birth of his child. He was tearful and objectively depressed. There was no suicidal ideation. He was commenced on an SSRI, sertraline 50mg, and referred for CBT. When reviewed after four weeks, he reported an improvement in his mood. He is awaiting psychology input.
The clinical syndrome of depression occurs when depressive symptoms become intense, persistent, pervasive, and affect day-to-day function. Clinical depression is also known as depressive disorder or major depressive disorder (MDD). A diagnosis of MDD depends on the presence of a number of specific symptoms over at least a two-week period, representing a change from previous functioning. Table 1 outlines DSM-V criteria for diagnosis of MDD. Severe MDD may be associated with psychotic features such as delusions and hallucinations, these are typically mood congruent.
MDD is common; 10-20 per cent of the population will have at least one episode during their lifetime and when it does occur, depression tends to be a recurrent disorder. Peak onset of MDD is in the third decade and MDD is twice as common in females, who have an earlier onset, more somatic features and more severe symptomatology.
MDD is associated with as much physical and social dysfunction as many other common medical illnesses. For example, the impairment of daily functioning associated with depression has been found to be significantly greater than the disability associated with arthritis, diabetes and coronary artery disease. In their estimation of global burden of illness, the World Health Organisation have predicted that by 2020 depression will be second only to ischaemic heart disease as a cause of disability world-wide.
Low grades of clinical depression characterised by depressive symptoms that affect day-to-day functioning, but not fulfilling the criteria for MDD, are also common. Such ‘subsyndromal’ depression may also have a significant impact on quality-of-life, functional impairment and healthcare utilisation and may often develop into MDD.
MDD in the medically unwell
MDD is the most common clinical psychiatric problem seen in medical patients; the prevalence of which is up to three-times higher than the general population. Some medical conditions are associated with higher rates of co-morbid depression. These include certain types of cancer, cardiovascular disease, chronic pain, and neurological illness. When depression does occur in the medically ill, a range of biological, psychological and socio-environmental factors may contribute to it.
Pre-morbid risk factors include female gender, family history of depression, and past history of childhood traumatic experiences. Illness-related factors especially associated with depression include severe disability, pain, endocrine disease, certain cancers, and treatment with interferon and corticosteroids. Receiving a medical diagnosis can be looked on as a stressful event that is followed by a period of psychological adjustment before return to psychological health. Failure to adjust appropriately may lead to depression. Factors that positively influence adjustment to illness include: Expanding social networks, seeking information, practical and social support, learning new skills, and emotion-focused coping.
The recognition of depression in this setting is important as depressive disorders adversely affect survival (including through suicide), length of hospital stay, cost of medical care, compliance with therapy, the ability to care for oneself and quality-of-life (Table 2). This has been most clearly demonstrated by Frasure-Smith and colleagues in Canada who first published evidence of more than a two-fold early increase in mortality among depressed patients compared to non-depressed patients post-myocardial infarction in 1993 (Figure 1). This finding is now well replicated in longer-term outcome studies and in other medical illnesses.
The possible biological mechanisms underpinning this effect of depression on medical illness outcome are becoming clearer. For instance, depression is associated with inter alia: Abnormal vagal tone, sympathoadrenomedullary dysfunction, hypothalamic pituitary adrenal axis dysfunction, immune system activation and enhanced platelet activation, factors which could directly influence cardiovascular morbidity
In spite of the effect of depression on medical outcome, it is well accepted that depression is under-recognised in medical settings. Physicians have been found to recognise depression in only a quarter to half of their depressed medical outpatients.
Factors inhibiting recognition of depressive disorder in medically ill patients include:
1. Depression can be difficult to identify in medically ill patients because the so-called ‘biological’ symptoms of depression are shared with physical symptoms of many medical illnesses. It is thus often clinically useful to place emphasis on the cognitive
features of depression. Difficulties also arise in certain neurological illnesses including Parkinsonian syndromes and stroke, in which the neurobehavioural effects of disruption to the frontal-subcortical circuitry may both mimic depression.
2. Depressed medically ill patients may communicate their distress poorly. The busy medical inpatient ward or outpatient clinic environment does not always facilitate good communication.
3. Healthcare professionals are typically overworked and biomedically focussed, attributes that tend to preclude adequate psychosocial enquiry.
4. Depression may be masked in medical illness and may present as a worsening of function, altered compliance with treatment or failed progress in rehabilitation.
5. While empathy is important in medical care, beware the tendency to over-empathise with patients. This may result in a failure to adequately distinguish depression that needs treatment, from an ‘understandable’ reaction to the stress of physical illness, (associated with appropriate and acceptable levels of distress) that does not need treatment.
6. Patients may be reluctant to disclose symptoms of depression because of the perception that they will be viewed and/or treated differently as a result. For some patients stigma may play a role.
Screening for depression in the medically unwell
There are a number of screening tools, which can help to detect depression (for example, the Beck Depression Inventory, the Hospital Anxiety and Depression Scale), all have limitations and none are a substitute for appropriate clinical enquiry by a vigilant healthcare professional. A simple two-question interview (Patient Health Questionnaire-2) has been found to be a highly sensitive screen tool, detecting more than 95 per cent of those with clinically significant depression (Table 3).
Treatment of depression in the medically unwell
Milder, uncomplicated and more short-lived depression can be managed with reassurance, advice, education and, where appropriate, drug therapy. In those with more severe symptomatology, suicidal ideation or in whom initial treatment has been unsuccessful, specialist referral to psychiatric services is indicated.
SSRIs are the first-line agents among the depressed medically ill. Of these, citalopram (10-40mg) and escitalopram (5-20mg) have least effect on the hepatic cytochrome P450 enzymes and thus have a lower potential for pharmacokinetic drug interactions.
There is good evidence supporting the safety of sertraline (50-200mg) in depressed patients with cardiovascular disease.
Paroxetine (10-50mg) may offer some advantage over others in depressed medical patients with irritable bowel syndrome (IBS) because of its anticholinergic effects.
Fluoxetine (20-60mg) should be avoided in depressed medical patients who are low/losing weight and such patients should be given dietary advice and/or vitamin supplementation along with antidepressant therapy. SSRIs may worsen migraine (in the same way that they worsen anxiety) during initiation of antidepressant therapy, an effect that usually wanes with time if tolerated. Sexual dysfunction is problematic with longer-term use.
Mirtazapine (7.5-45mg), a presynaptic alpha-2 adrenoceptor antagonist, has few drug interactions and is especially useful for the early target symptoms of nausea, anorexia, and insomnia. Weight gain and fatigue may limit its longer-term use.
Agomelatine (25-50mg) is an M-1/M-2 receptor agonist. It is useful in patients in whom disturbed sleep is problematic. Agomelatine is associated with less weight gain and sexual side-effects than other antidepressants. Risk of hepatic adverse effects requires monitoring of LFTs prior to initiation and during treatment.
Venlafaxine (37.5-375mg) is reserved as a second-line agent as it may be more effective but less well tolerated than SSRIs. It should be avoided in heart disease and epilepsy.
In patients with chronic pain (including migraine) and depression, amitriptyline (25mg-150mg) remains the antidepressant of choice. It is especially effective in severe and agitated depression and its antimuscarinic effect may also assist with bowel symptoms in IBS patients. However, amitriptyline is potentially cardiotoxic, unsafe in overdose, impairs cognition and may induce delirium in older, medically ill patients. Venlafaxine and duloxetine (up to 120mg) can be helpful in those with symptoms of chronic pain.
Psychological and social interventions have a role in management of depressed medically ill patients. Empathic listening and reassurance around the common reactions to the losses and threats posed by medical illness is important. Education about the illness itself may alleviate unfounded worry and fears. A problem solving approach helps patients manage practical aspects of life stress. The benefits of maintaining/expanding social networks is emphasised sometimes by facilitating involvement with specific illness support agencies. One of the most commonly employed psychological interventions is that of cognitive behavioural therapy (CBT), the principles of which can be applied to correct distorted thinking and encourage appropriate coping strategies. CBT has been shown to be as effective as antidepressant drug treatment in cases of mild-moderate depression and may be especially useful in medical patients.
Depression is common in medically unwell patients and is associated with significant morbidity. Increased awareness of, and detection of depression in this cohort, with subsequent effective treatment can lead to a reduction in overall morbidity and mortality. When prescribing antidepressant medication, it is important to be aware of interactions from both a pharmacological or illness perspective.