# 26.5.6 Depressive disorder 6493 Joseph Cerimele an # 26.5.6 Depressive disorder 6493 Joseph Cerimele and Lydia Chwastiak 26.5.6  Depressive disorder 6493 who then resume use on discharge, may re-​establish levels of tol- erance and vulnerability to withdrawal much faster than they ori- ginally did. For patients frequently admitted to hospital, the cycle of detoxification and re-​toxification is probably more harmful than agreeing a more regular substitute prescription regimen, though this is best undertaken by a specialist substance misuse service rather than in a medical clinic. Communication with relapse prevention programmes run by substance misuse services is also important for newly abstinent patients on discharge from medical wards. Some hospitals employ drug liaison nurses who act as the link between medical and substance misuse services, ensuring clear communica- tion, consistency in prescribing, and proactive follow up. Attempts to obtain the drug of misuse The salience of and craving for the drug of dependence can lead to some of the most difficult substance misuse problems encountered on medical wards. A patient’s desire to obtain a drug of addiction can be so strong as to outweigh all other considerations, leading to them taking major risks with their physical health. Such patients can pressurize ward teams to prescribe inappropriately and may not adhere to medical advice. Some patients will self-​discharge from hospital to obtain drugs, while others may bring drugs into the ward or arrange for them to be delivered. Patients with direct venous access (peripheral cannulae, cen- tral lines) may misuse these to self-​administer illicit drugs. These risks are greatest in patients who are mobile and face lengthy admissions, as in those on intravenous antibiotics for infectious endocarditis. Such cases can try the patience of medical teams and may raise the question of legal interventions, via common law, mental health, or in- capacity legislation. How such cases are managed will vary between jur- isdictions, hence it is important for medical teams encountering such cases to understand what the local law permits, requires, and prevents. For example, in the three United Kingdom jurisdictions, drug depend- ence in itself is excluded as grounds for applying incapacity measures or detention under the mental health act (although abnormal mental states arising from drug use are not). It is generally preferable to avoid recourse to legal measures and to offer discussion with the patient, their family, and relevant drug misuse and psychiatry services. The guiding principles behind management should be openness of discussion, clarity of communication, consistency within and between teams, willingness to set limits, and firmness in applying them. Even when all these principles are adhered to, there will be cases where patients take their own discharge to the detriment of their health, and others where they might be asked to leave the hos- pital, or even be arrested within it. Where the risks accrue to someone other than the dependent user, such as a child, or a fetus, it can be particularly difficult to strike the balance between intervening too little and too late, and thereby allowing harm to arise, and intervening too strongly or precipi- tately and thereby causing it. Liaison with social workers, obstetric services, and substance misuse specialists is therefore important. FURTHER READING Department of Health (England) (2007). Drug misuse and depend- ence: UK guidelines on clinical management. Department of Health (England), London; the Scottish Government, Welsh Assembly Government, and Northern Ireland Executive. National Institute for Health and Clinical Excellence (NICE) (2007). Drug misuse:  opiate detoxification. NICE clinical guideline 52. National Institute for Health and Clinical Excellence, London. Royal College of Psychiatrists (2014). One new drug a week: why novel psychoactive substances and club drugs need a different response from UK treatment providers. Royal College of Psychiatrists, London. World Health Organization (2010). Mental and behavioural disor- ders due to psychoactive substance use (F10-​F19) in International Statistical Classification of Diseases and Related Health Problems, 10th revision (ICD-​10). World Health Organization, Geneva. 26.5.6  Depressive disorder Joseph Cerimele and Lydia Chwastiak ESSENTIALS Depression is a common psychiatric illness seen by physicians. It not only greatly impairs quality of life, but also frequently complicates chronic medical conditions such as diabetes. Despite being common and clinically important it is frequently insufficiently treated, hence it is important to seek the symptoms of depression in all patients with chronic medical conditions. When found, the physician has an im- portant role in explaining the nature of depression and its treatment to the patient. Treatment is with antidepressant drugs and/​or psy- chological treatment. When assessing depressed patients, it is always important to assess for suicide risk. Complex cases, failure to respond to initial treatment, or concern about suicide risk, indicate the need for referral to a psychiatrist. Introduction Depression is now the leading cause of disability worldwide. The World Mental Health Survey, conducted in 17 countries, found that 1 in 20 people reported having suffered an episode of depression in the previous year. Depressive disorders typically start at a young age and are often recurrent or chronic. They have a severe negative effect on quality of life (affecting individuals’ ability to work and form re- lationships), have adverse effects on co-​morbid medical illness, and increase the risk of suicide. Although efficacious and cost-​effective treatments are available, most people do not receive them. Barriers to effective treatment include both a failure to diagnose depression and a failure to provide effective treatment. Aetiology Depression is the product of interactions between genetic vulner- ability and environmental exposures. The concordance rate for depression among monozygotic twins was 37% in a large Swedish study of over 15 000 sets of twins, indicating genetic vulnerability. Depression is also more likely to develop after negative life stresses SECTION 26  Psychiatric and drug-related disorders 6494 and in those who lack social support. There is a strong association with living in an area of social deprivation. Physiologically, de- pression is associated with dysregulation of noradrenaline (nor- epinephrine), serotonin, and dopamine and dysfunction of the hypothalamic–​pituitary–​adrenal (HPA) axis. Epidemiology The lifetime prevalence of major depressive disorder in Western countries is approximately 13%, with a 12-​month prevalence of 5%. The prevalence is higher among women, probably because of both biological (endocrine), and sociocultural factors. Depression is a recurrent illness; more than three-​quarters of those who ex- perience a major depressive episode will experience a subsequent episode. Almost half of patients with major depressive disorder have co-​ morbid anxiety disorders, and many have coexisting substance use problems. In the United States, the estimated total annual cost of major depressive disorder was $210.5 billion in 2010, with approximately 45% attributable to direct costs, 5% to suicide-​related mortality costs and 50% to workplace costs. Co-​morbid medical conditions account for the largest portion of the growing economic burden of major depressive disorder. Persons with cardiovascular disease, diabetes, and other chronic medical conditions have an increased risk of major depressive dis- order that complicates the management of the medical condition (Table 26.5.6.1 and Fig. 26.5.6.1). Clinical features Depressed mood and anhedonia (loss of interest and pleasure) are the two cardinal symptoms of depression. At least one of these must be pre- sent for at least two weeks for a diagnosis of major depressive disorder. The diagnosis requires five or more of the following nine symptoms. • Feeling depressed, sad, or hopeless most of the time (depressed mood) • Loss of interest or pleasure in activities (anhedonia) • Change in appetite and/​ or weight loss or gain (change of >5% of body weight in a month) • Sleeping more or less than usual (insomnia or hypersomnia) • Physical restlessness (psychomotor agitation) or slowed move- ments (psychomotor retardation) • Fatigue or loss of energy • Frequent feelings of worthlessness, or excessive or inappropriate guilt • Diminished ability to concentrate or make decisions • Recurrent thoughts of death or suicidal thought, plans, or an attempt Table 26.5.6.1  Twelve-​month prevalence of major depressive disorder in patients with chronic medical conditions Population 12-​month prevalence Community 3–​5% Primary care 6–​10% Cardiovascular disease 15–​23% Diabetes 12–​18% Chronic pain 33–​35% Unhealthy behaviours—binge eating, smoking, etc... Stress of diabetes management Poor symptom control Difficulty in exercising/exhaustion Complications of medical illness Mortality DEPRESSION DIABETES Difficulty in making dietary changes Lack of social interaction Lack of adherence to medication Lack of motivation to exercise/obesity Psychophysiologic: Insulin sensitivity, autoimmune nervous system inflammatory makers, cortisol Fig. 26.5.6.1  Bidirectional adverse effects of depression and diabetes. 26.5.6  Depressive disorder 6495 Almost half of patients with depression do not have their depres- sion diagnosed. It is important to remember that most patients with depression initially present with physical complaints such as fatigue or poor sleep, rather than with low mood. Because the diagnosis is often missed, active screening for depression has been recommended. The Patient Health Questionnaire-​ 9 (PHQ-​9) is a self-​rated scale widely used to screen for de- pression and to monitor response to depression treatment (Fig. 26.5.6.2). Treatment Patients with depression require timely, evidence-​based treatment. Mild depression benefits from either a psychological intervention or an antidepressant medication, and moderate or severe depres- sion from a combination of antidepressant medication and a high-​ intensity psychological treatment. The first step in treatment is to educate patients about the nature of depression and its treatment. A collaborative approach with the PATIENT HEALTH QUESTIONNAIRE-9 (PHQ-9) Over the last 2 weeks, how often have you been bothered by any of the following problems? (Use “ ” to indicate your answer) 1. Little interest or pleasure in doing things Not at all 0 1 2 3 0 1 2 3 0 1 2 3 0 1 2 3 0 1 2 3 0 1 2 3 0 1 2 3 0 1 2 3 0 Not difficult at all Somewhat difficult Very difficult Extremely difficult FOR OFFICE CODING If you checked off any problems, how difficult have these problems made it for you to do your work, take care of things at home, or get along with other people? 0 + + + = Total Score: 1 2 3 Several days More than half the days Nearly every day 3. Trouble falling or staying asleep, or sleeping too much Feeling tired or having little energy Poor appetite or overeating 4. 5. Feeling bad about yourself—or that you are a failure or have let yourself or your family down 6. Thoughts that you would be better off dead or of hurting yourself in some way 9. Moving or speaking so slowly that other people could have noticed? Or the opposite—being so fidgety or restless that you have been moving around a lot more than usual 8. Trouble concentrating on things, such as reading the newspaper or watching television 7. Feeling down, depressed, or hopeless 2. Fig. 26.5.6.2  The Patient Health Questionnaire-​9, a behavioural health measure for screening for depression and monitoring response to treatment. Developed by Drs. Robert L. Spitzer, Janet B. W. Williams, Kurt Kroenke, and colleagues. SECTION 26  Psychiatric and drug-related disorders 6496 patient works best and can increase the patient’s sense of participation in their care, leading to better subsequent adherence to treatment. Several factors influence the choice of treatment: • Duration of the episode of depression • Previous course of depression and response to treatment • Likelihood of adherence to treatment and any potential adverse effects • The patient’s treatment preference Psychotherapy Three effective forms of short-​term psychotherapy or talking treat- ment commonly used for depression are cognitive behavioural therapy, interpersonal psychotherapy, and problem-​solving therapy. Cognitive behavioural therapy addresses negative and distorted thinking patterns and related behaviours that often accompany de- pression. Behavioural activation is a simpler type of cognitive be- havioural therapy that aims to help the patient regain important activities. Interpersonal psychotherapy targets current interpersonal relationship difficulties that contribute to the development and per- sistence of depressive symptoms. Problem-​solving therapy is a col- laborative treatment in which patient and therapist break down life problems into smaller, solvable units, and address them one at a time. Antidepressant medications Antidepressant medications are all of similar efficacy in the treatment of outpatients with major depression. Medication choice is therefore based on factors other than efficacy, such as side effects, history of re- sponse, or a failure in the individual or a family member, possible drug interactions, psychiatric or medical co-​morbidity, and patient age. The selective serotonin reuptake inhibitors (SSRIs) are usually the first-​line treatment due to their tolerability (Table 26.5.6.2). It should be noted, however, that most SSRIs inhibit the cytochrome P450 system in the liver; paroxetine and fluoxetine have the greatest potential for drug interactions. Common side effects of SSRIs include anxiety, insomnia, nausea, and headache. However, these occur to a problematic degree in fewer than 20% of patients. Monitoring treatment response Brief reviews every 2 weeks are needed during the first 6 weeks of treatment to evaluate side effects of medications and review the dosage. Treatment response should be assessed after 4 weeks of a therapeutic dose of medication. Self-​rating scales (such as the PHQ-​ 9) administered at initial diagnosis and at each follow-​up offer a simple way to monitoring response. A 25% or greater reduction in baseline symptoms constitutes a reasonable basis for extending the initial treatment. If there has been no response or only a partial re- sponse, the dose should be increased to the upper therapeutic range. For patients who still do not respond to treatment, it is im- portant to: • check adherence to, and side effects from, initial treatment; • increase the frequency of appointments using outcome monitoring; • consider re-​introducing previous treatments that have been inad- equately delivered or adhered to; • consider switching to an alternative antidepressant; • consider combining with a second drug or augmenting the first drug. A change in treatment after non​response (either switching to dif- ferent SSRI or different class of antidepressant or combining the first drug with another drug such as mirtazapine) leads to an additional 20% of patients responding. A second change in treatment (either augmentation or switching) is effective in an additional 10–​15% of patients. Switching antidepressants Switching to another antidepressant can be done within one week when switching from drugs with a short half-​life. However, the potential for interactions should be considered when determining the choice of new drug and the duration of the transition. Switching may be to a different SSRI or to a newer-​ generation antidepressant (serotonin–​norepinephrine reuptake inhibitor or mirtazapine). Combining and augmenting medications Combination treatment is combining two antidepressants, such as when mirtazapine is added to SSRI treatment. The use of com- binations of medications may be needed in some patients, but increases the risk of potential medication interactions and side effect burden, and may require specialist advice. Augmentation involves the use of a non-​antidepressant medication (lithium, aripiprazole, quetiapine, and thyroxine) with an antidepressant. Continuation and maintenance therapy Once recovered from the depressive episode, patients should con- tinue medication treatment for at least nine months to minimize the risk of relapse; approximately 40% of remitted primary care patients suffer relapse. Stopping treatment Treatment with antidepressant drugs should generally not be sud- denly discontinued; almost all antidepressants (except fluoxetine) can produce discontinuation symptoms (sleep disturbance, anxiety, memory disturbance, malaise, muscle aches, vertigo, sweating, and gastrointestinal upset). Discontinuation is therefore done by redu- cing the dose gradually over several weeks. Collaborative care Collaborative care is a system of care in which a psychiatrist col- laborates with a primary care physician, aided by a case manager. It is effective in achieving cost-​effective delivery of both drug and psychological treatments for depression. Table 26.5.6.3 list the prin- ciples of collaborative care. Other treatments Electroconvulsive therapy (ECT) remains the most effective treat- ment available for very severe or psychotic depression. Some re- versible short-​term memory loss is a common side effect, but this reverts to normal in almost all cases. Patients with recurrent depres- sion who receive effective ECT treatment need prophylactic medi- cation or maintenance ECT once the acute course of the treatment has finished. Meta-​analyses of randomized-​controlled trials suggest that re- petitive transcranial magnetic stimulation has short-​term anti- depressant properties. 26.5.6  Depressive disorder 6497 Outcome Depression is typically a chronic or recurrent illness. Half the patients who have had a single major depressive episode will have a second one; 70% of those who have two episodes will have a third; and 90% of those who have had three episodes will have a fourth. The number of previous episodes of depression, presence of re- sidual symptoms, and co-​occurring health problems and social diffi- culties increase the risk of recurrence. Patients at risk for recurrence should continue antidepressant medications at the dose used to achieve remission for at least two years. The potential for severe con- sequences from recurrent depression, including suicide, are strong reasons to maintain antidepressant therapy. The risk of suicide is 10 times greater in patients with depression compared to the general population; suicide risk should therefore be assessed in all patients with depression. Most people who complete suicide have presented to their primary care physician within a month of their death. Older white males are at highest risk, and alcoholism, severe medical illness, psychosis, and lack of social support are additional risk factors. Asking about suicide will not increase a patient’s risk. Enquiries about suicide can re- assure the patient and enable the physician and patient together to make a plan to prevent suicide, including deciding together whether emergency psychiatric consultation or hospitalization is necessary. There is an increased risk of thoughts of suicide in the first 28 days after starting and stopping antidepressants, so careful monitoring of patients during these periods is required. Advise a person with de- pression and their family to be vigilant for mood changes, negativity and hopelessness, and suicidal ideation, and to contact their practi- tioner if concerned. Table 26.5.6.2  Overview of commonly used antidepressant medications Medication Common starting doses Therapeutic dose Class Advantages Disadvantages Citalopram 10 mg/​day 20–​40 mg/​day SSRI Fewer medication interactions 40 mg is the maximum dose as higher dose increases risk of prolonged QTc Escitalopram 5 mg/​day 10–​20 mg/​day SSRI Fewer medication interactions; less likely to cause sexual side effects More expensive than citalopram Fluoxetine 10–​20 mg/​day 20–​80 mg/​day SSRI Longer half-​life makes tapering unnecessary (good for patients with inconsistent adherence); relatively weight neutral More CY P450 interactions Paroxetine 10–​20 mg/​day 20–​60 mg/​day SSRI Sedating effects helpful for anxiety and insomnia Gastrointestinal side effects; anticholinergic effects increase fall risk and confusion in older people Sertraline 25–​50 mg/​day 100–​200 mg/​day SSRI Safe to use post-​MI Few Mirtazapine 7.5–​15 mg /​day 30–​45 mg/​day SNRI at therapeutic dose Sedating effects helpful for anxiety and insomnia Sedation; increased appetite and weight gain Venlafaxine 37.5–​75 mg /​day 150–​300 mg/​day SNRI Helpful for neuropathic pain; XR version can be taken once daily Risk of increase diastolic blood pressure; short half-​life can cause an uncomfortable discontinuation syndrome Duloxetine 20 mg /​day 60–​90 mg/​day SNRI Effective for treatment of peripheral neuropathy and fibromyalgia Dose adjustment for CrCl <30 ml/​min; expensive SNRI, serotonin–​norepinephrine reuptake inhibitor; SSRI, selective serotonin reuptake inhibitor. Table 26.5.6.3  Core principles of collaborative care Core principle Definition Patient-​centred team care Primary care and psychiatrists collaborate using shared care plans that incorporate patient goals. Population-​based care Care team shares a defined group of patients tracked in a registry to ensure no one falls through the cracks. Measurement-​based treatment to target (or stepped care) Each patient has a target; progress toward this is monitored and treatment changed if patients are not improving. Evidence-​based care Patients are given evidence-​based care (both drugs and psychotherapies).