The first step in the diagnosis of geriatric depression is to obtain a detailed history. It’s always challenging to get a clear cut symptom profile of depression in old age. Geriatric depression mainly presents with an atypical presentation with somatic symptoms like aches and pains in the body, difficulty sleeping, decreased cognition, which makes it even challenging to diagnose. The next step is to have a thorough mental status examination and formal cognitive testing to rule out dementia. On the mental status examination, the patient would have decreased psychomotor activity, and speech would be slow. In severe forms, the patient would express thoughts of self-blame and guilt. Here it is imperative to inquire about any homicidal or suicidal ideations/plans. The clinician should always ask the patient about access to firearms. Conduct neuropsychological testing if needed. Physical examination to rule out any medical or neurological disorder should be part of the total workup. Various specific scales also merit consideration for the geriatric population—Patient Health Questionnaire 2 (PHQ-2),[12] Geriatric Depression Scale— It's a 30 item scale with a yes/no response, which is self-administered by the patient. The questions are designed to test the mood, energy level, loss of interest in pleasurable activities, guilt feelings, hopelessness, worthlessness, and suicidal ideations. Each question gets a score of 0 or 1 points. Based on the total score, it is categorized as normal (0 to 9), mild depression (10 to 19), or severe depression (20 to 30).

Depression is a complex phenomenon with an increasing number of morbidity and mortality. It is always necessary to rule out specific treatable, reversible causes before we formulate the management plan. In this regard, laboratory testing is necessary before considering a diagnosis of major depressive disorder. This workup includes routine lab work like CBC and CMP, urine toxicology, vitamin B12 levels, folate levels, and TSH. rapid plasma reagin/venereal disease testing, human immunodeficiency virus testing, as well as neuroimaging studies like CT scan and MRI scan of the brain may be indicated depending on the history and presentation.

Comorbid dementia and other neurocognitive disorder pose ethical challenges in the treatment of depressed elderly. It affects their ability to make informed consent, and detailed evaluation must take place for testing decisional capacity in the elderly before we begin treatment.

Psychotherapy in the form of cognitive behavior therapy and interpersonal therapy is the first-line treatment of mild depression.[13] Other types of treatment, like psychodynamic therapy and supportive therapies, have been found to be effective. In moderate to severe forms of depression, pharmacotherapy is a recommended approach, and in chronic depression, a combination of pharmacotherapy and psychotherapy is considered to be the most effective. 

Pharmacotherapy: Many brain systems malfunction in major depression, and no single cause has been identified. However, the treatment of malfunctioning biogenic amine systems in the brain, especially the serotonergic systems, relieves symptoms in many individuals. In the elderly population, we need to ’start low and go slow’ with the drug dosage and titration, keeping in mind the metabolic changes with aging pharmacodynamics and pharmacokinetics in old age. There occurs alteration in the enzymes and neurotransmitters—Increased monoamine-oxidase, decreased acetylcholine, decreased dopamine, receptors decrease in number, increased resistance to drug diffusion along with declining hepatic function, absorption, renal excretion and distribution with age, which makes pharmacotherapy even more challenging in the elderly. The following class of drugs has shown promising results in treating depression:

• Selective Serotonin Reuptake Inhibitor (SSRI):

In adults with depressive disorder, SSRI is considered the first line and is safe in the elderly, due to better tolerability and easy to use. SSRI typically takes four to six weeks to have full effect. It can take longer than six weeks as well. Special mention of side effects in the elderly includes hyponatremia, akathisia, anorexia, and sinus bradycardia.[14] When started on SSRI, it is essential to monitor for suicide risk, though in the long term, they reduce the risk of suicide.[15] Depression of severe form has shown promising results with other drugs and electroconvulsive therapy. Citalopram causes QT prolongation in a dose-dependent manner, thereby leading to arrhythmias.[16] The recommended dose is 20 mg/ day should not exceed in patients greater than 60 years of age. The common side effects include gastrointestinal distress (nausea, diarrhea), anxiety, and sleep disturbance.[17]

•  Serotonin-norepinephrine Reuptake Inhibitors (SNRI):

These are considered as the second-line treatment and include venlafaxine, desvenlafaxine, and duloxetine. This group of medication is thought to be safe in the elderly population. This class of the drug has a dual-action and found to be useful in patients with comorbid pain. The SNRI includes the risk of diastolic hypertension based on dose. Both SNRI and SSRI can cause the typical triad of altered mentation, autonomic changes, and neuromuscular excitation causing serotonin syndrome.[18] A systematic review indicated dual-action antidepressants like SNRI and tricyclic antidepressants have no superiority over single-action antidepressants like SSRI concerning safety profile and efficacy.[19]

•  Atypical Antidepressants:

These include bupropion and mirtazapine. Mirtazapine is also a second-line agent. Besides antidepressant action, it is also useful in patients with insomnia, anorexia, and restlessness. When comparing mirtazapine with paroxetine, the tolerability profile was similar. Common side effects include sedation, increased appetite causing weight gain, dry mouth, and constipation. Noradrenergic effects are more pronounced over the anti-histaminergic effects at higher dosages and thus lower sedative effects. In patients with symptoms of lethargy or fatigue, bupropion is thought to be an activating agent. Bupropion tends to lower the seizure threshold and is contraindicated in patients with a seizure disorder, concurrent use with CNS depressants, alcohol detoxification, and diagnosis of bulimia nervosa.

•  Tricyclic Antidepressants (TCA):

This class of drugs is efficacious, though no longer considered first or second-line agents. These agents may be useful for treatment failure with other antidepressants. Secondary to their action on multiple receptors, TCAs are believed to have various side effects. When compared with in the same class, secondary amines (desipramine and nortriptyline) over tertiary amine (imipramine and amitriptyline) are safer regarding the side effect profile. Given the increased risk of suicide in the elderly population, TCA can cause a lethal overdose. These are the only drugs that are seen to reduce the risk of relapse after Electroconvulsive therapy and possibly have superior efficacy in patients with melancholic depression. Side effects include weight gain and sedation due to histamine receptor effects. Alpha-adrenergic receptor action leads to orthostatic hypotension and tachycardia, while the muscarinic receptor effect causes dry mouth, dizziness, and visual problems that include narrow-angle glaucoma, urinary retention, and constipation.

•  Monoamine Oxidase Inhibitors (MAOIs):

MOAI’s are rarely used owing to their special dietary restrictions to prevent adrenergic crisis and serotonin syndrome. This drug class has limited studies in the elderly population, though they are proven to be beneficial in atypical depression. Common side effects include orthostatic hypotension, activation, and insomnia. 

•  Electroconvulsive Therapy (ECT):

Enormous data supports the fact that ECT is the treatment for depression resistant to psychotherapy and/pharmacotherapy. ECT is of two kinds, unilateral and bilateral. The two methods do not have any difference in efficacy, though, for long term treatment (greater than or equal to 3 weeks), bilateral is the chosen option, and for short term, (less than or equal to 5 weeks) treatment unilateral is preferable. Hypertension and tachycardia are the cardiovascular side effects that may occur, though these are transient. Other common side effects are amnesia and headache. 

•  Other Brain Stimulation Techniques

These include repetitive transcranial magnetic stimulation (rTMS), deep brain stimulation (DBS), and vagus nerve stimulation (VNS). However, these techniques do not have randomized studies in the elderly population.

• Other Treatment Modalities

Research has demonstrated that a healthy diet, exercise, and meditation helps with the prevention and treatment of mild depression in the elderly. Diet rich in omega-3 fatty acids and fish oil have been found to improve depression.

• Dementia—Late-onset depression, when presented as cognitive deficits as the primary symptom, can be confused with dementia in the elderly. Detailed mental status examination and cognitive testing should take place before making the final diagnosis.[5] According to the Diagnostic and Statistical Manual of Mental Disorders (DSM-5), other differentials could be:
• Episodes of mania with mixed or irritable symptoms—symptoms of depression presented as irritability, anger outbursts can mimic a manic episode.
• Mood disorder due to another medical condition—depression should be diagnosed only when the symptoms are not a direct pathophysiological consequence of a specific medical condition, for example, multiple sclerosis, stroke, hypothyroidism.
• Substance/medication-induced depressive disorder—If the depressive disorder is secondary to substance/medication use, the symptoms fade away after stopping the suspected substance or medicine, and the effect wears off.
• Adjustment disorder with depressed mood— The full criteria for a major depressive episode are not met in adjustment disorder.
• Sadness— Intervals of sorrow are inherent traits of the human experience; this should not be interpreted as a major depressive episode unless it fulfills the depression criteria. 

Depression was traditionally considered as a self-limiting and curable illness. After the depressive phase was over, patients were expected to revert to a pre-morbid level of normal functioning. Management was done on ‘as and when’ required basis. Long-term treatment was not encouraged. Without treatment, depression tends to assume a chronic course, be recurrent and associated with increased disability.[20] In comparison with other chronic diseases like diabetes, asthma, angina, and arthritis, depression impairs health status to a greater degree.[21] Co-morbidity with depression worsens the health status of people with chronic diseases. Recurrence is more common if symptoms of depression do not receive adequate treatment. Current guidelines recommend continuing antidepressants for 4 to 6 months after remission to prevent relapse. After improvement, 50% relapse within one year and most within two years. Those who had one episode of depression 50-85% will go on to have the second episode of depression. About 80 to 90% of those who had the second episode of depression will go on to have a third one. Around 90% with severe depression experience recurrence.[22] There is evidence that chronic depression is more familial, more refractory to treatment, and more impairing than episodic major depression. Poor prognostic factors can categorize as patient factors and illness factors:

Patient factors are:

• 1. Family history of affective disorder
• 2. Pre-existing dysthymias
• 3. Comorbid anxiety disorder
• 4. Comorbid substance abuse
• 5. Low T3 level

 Illness factors are:

• 1. Previous depressive episode
• 2. Longer and severe index episode
• 3. Residual sub-syndromal depression
• 4. The first episode after the age of 60
• 5. Seasonal pattern

Depression is associated with substantial disability. It often occurs in the presence of another mental disorder, and this co-morbidity leads to severe complications for the depressive episode.[20] Co-morbidity predicts more prolonged and more severe episodes of depression, increased risk of chronicity, interference with life and activities, hospitalization, and suicide attempts. It also interferes with the course of depressive disorder. It is an important factor in the assessment and treatment of a depressed patient. Common comorbid anxiety disorders are simple phobia, social phobia, generalized anxiety disorder, post-traumatic stress disorder, agoraphobia, panic disorder, substance-use disorders, alcohol dependence, and other drug dependence.[23] Another major complication of depression is thoughts of ending one’s life. Suicide rates are highest in the elderly—25% of all suicides are elderly. The probability increases in elderly white males; isolation further increases the risk. Common predictors of suicide risk include age, male separated widowed, isolated divorced, debilitating illness, substance abuse. Depression also increases the chances of medical co-morbidity in the elderly—cardiovascular disorders,[24] diabetes, dementia, stroke, stress ulcers, and, eventually, the development of cancer.[25]

The increasing number of older adults brings a growing number of late-age mentally ill. Conditions such as dementia, delirium, and old-age depression not only cause disability among their victims, they diminish the quality of life and impose an increased burden on the family and other care providers. Among the neuro-psychiatric conditions, dementia and major depression are the two major contributors to all disability-adjusted life years (DALY) in the geriatric age group. Therefore, global aging has profound implications for social, economic, and health policy. Depression is associated with many physical illnesses and affects their development and course. Therefore, awareness about the symptoms and signs of depression is necessary for patients and caregivers, which would help them to seek early treatment and management, and prevent putting their lives in jeopardy.

Late-onset depression frequently poses a diagnostic dilemma. These patients may exhibit non-specific signs and symptoms such as somatic complaints- pain abdomen, generalized body ache, anger outbursts, irritability, decreased cognition. It may be due to several causes with different etiologies. While history may reveal that the patient has depression, the cause is difficult to know without detailed mental status examination, cognitive testing, and laboratory investigations. For the timely diagnosis and management of late-onset depression, a collaborative interprofessional effort is necessary. For example, if an elderly patient complains of persistent pain in the abdomen despite normal routine investigations and adequate treatment with medications by a physician, he should consider the differential of late-life depression in mind before ordering further rigorous laboratory investigations as this could be an early sign of depression. Another common concern in the elderly is of polypharmacy and drug interactions. The pharmacist should regularly monitor the medications and communicate with the clinician if there are any potentially harmful medications. Some medications can worsen or cause a depression that comprises antihypertensive, antiparkinsonian, anticancer, hormonal agents, and benzodiazepines. Finally, a mental health nurse and a social worker should be involved in the outpatient care of these patients as many need support services, a safe living environment, and understanding caregivers. An interprofessional team approach is vital if one wants to improve outcomes and minimize untoward events associated with severe depression. [Level 5]