Differential Diagnosis: Delirium, Dementia, and Depression

The risk of delirium increases with hospitalization, the number and severity of medical issues, and advanced age. The prevalence of delirium is approximately 14% of individuals over 85 years of age. For hospitalized individuals, delirium is associated with a 40% mortality rate within a year of diagnosis (APA, 2013). Prevalence rates of delirium for older adults in various settings or situations are presented below. 

Settings or Situations and Prevalence Rates

• In Emergency Departments: 10%-30%
• In the Hospital: 6%-56%
• After Surgery: 15%-53%
• In Intensive Care Units: 70%-87%
• In Long-Term Care Facilities: 60%
• At End-of-Life: 83%

(APA, 2013 and Kiliçaslan et al., 2022)

Hyperactive, hypoactive, and mixed levels of activity categorize delirium. Hyperactive presentations are manifested by labile mood, agitation, and lack of cooperation, pose safety risks for individuals with delirium and their caregivers, and are often associated with or result from reactions to substances or medications. Hypoactive presentations are manifested by sluggishness, lethargy, and stuporous state and occur more commonly in older adults than in younger persons. Mixed presentations are manifested by normal activity with disturbances in attention and awareness or by rapidly fluctuating activity, which is switching between hyperactive and hypoactive states (APA, 2013; Dening & Aldridge, 2021).

Delirium is always characterized by disturbance in attention or awareness that is associated with a change in baseline cognition. Disturbances of attention are reflected by a decreased ability to direct, focus, maintain, or switch attention. Disturbances of awareness are reflected by decreased orientation to a situation, time, place, or person. Alternations of the sleep-wake cycle often occur and may include daytime somnolence and nighttime wakefulness. Emotional and perceptual shifts and disturbances may manifest in anxiety, irritability, agitation, screaming, moaning, muttering, and hallucinations (APA, 2013).

Early identification and treatment shorten the duration of delirium.The Confusion Assessment Method (CAM) is the most widely used delirium assessment tool and has a high sensitivity (94%–100%) and specificity (90%–95%). Using CAM, a diagnosis of delirium can be made if an older adult exhibits an acute change in mental status, with fluctuating symptoms and inattention with, either disorganized thinking or an altered level of consciousness (Inouye et al., 1990; Kiliçaslan et al., 2022). The Delirium Observation Screening Scale and the Neecham Confusion Scale are also valid and reliable measures (Neelon et al.‚ 1996; Schuurmans et al. 2003). Instruments used to assess delirium are the following

The Confusion Assessment Method (CAM) is a 9-item scale that is the gold standard for delirium assessment. To score it, the patient must have the presence of acute onset and fluctuating discourse and inattention AND EITHER disorganized thinking OR an altered level of consciousness.

The Delirium Observation Screening Scale (DOS) is a 13-item observer-rated scale. A score of 4-13 indicates the presence of delirium. A score of 0-3 indicates no delirium present. 

The Neecham Confusion Scale is a 9-item observer-rated scale.  A score of:

• 27-30 is not confused; normal function
• 25-26 is not confused but at high risk of confusion
• 20-24 is mild to early development of confusion
• 0-19 is moderate to severe confusion

Delirium is a disturbance in attention and awareness that develops over a short period, represents a change in baseline attention and awareness, and fluctuates in severity throughout the day. At least one other cognitive disturbance, such as problems with language, learning, memory, orientation, perception, and visuospatial capability, must also be present. Symptoms must not be better explained by another existing or developing neurocognitive disorder or the presence of a significantly reduced level of arousal, such as a coma. Delirium is a physiological consequence of a medical situation, substance intoxication or withdrawal, or exposure to a toxin (APA, 2013; Dening & Aldridge, 2021).

Specifications that should be included with a diagnosis of delirium include duration, type, substance, medication, or medical condition. When diagnosing delirium, the specification of acute (hours or days) or persistent (weeks or months) should be listed. Additionally, delirium, hyperactive, hypoactive, or mixed should be included. If delirium is associated with a substance, the specific substance, severity of the substance use, and whether the individual is intoxicated or in withdrawal should be identified. If delirium is associated with a medication or medical condition, the name of the medication or medical condition should be listed (APA, 2013).

When delirium is identified, determining and treating the physiological cause of delirium is the highest priority. Additionally, ensuring safety is paramount as the older adult may be unable to protect their safety. Behavior may be unpredictable, so communication with the older adult with delirium should be calm, focused, and clear (Carey et al., 2022; Dening & Aldridge, 2021).

When looking for a cause of delirium, assess for dehydration and ensure the individual is adequately hydrated (Beck et al., 2021; Carey et al., 2022). Then, consider the possibility of a urinary, respiratory, or other infection. Although they may have an infection, older adults’ temperature may be within normal limits or low. Once an infection has been ruled out, evaluate the person’s medications to determine if a medication could be causing delirium. Identify whether a medication was added or the dose of an existing medication was adjusted. Consider interactions of medications or whether the person’s physiological status may have changed, predisposing them to adverse medication effects. Once dehydration, infection, and medication issues have been ruled out, then consider other possible causes of delirium, such as decreased oxygenation, metabolic issues, and environmental changes. When the cause of the delirium has been identified and treated, the delirium will resolve (Carey et al., 2022; Dening & Aldridge, 2021; Lind et al., 2022).

Individuals with delirium may be agitated, so ensure that they do not hurt themselves or someone else and that their baseline bodily needs, such as hydration, nutrition, and elimination, are met. One-to-one supervision or pharmacological management with an antipsychotic may be required, especially for hyperactive or mixed presentations (Carey et al., 2022; Dening & Aldridge, 2021).

Dementia is an umbrella term for a variety of progressive diseases that generally affect older adults and cause significant cognitive decline. Types of dementia include Alzheimer’s disease, frontotemporal lobar degeneration, human immunodeficiency virus (HIV) infection, Huntington’s disease, Lewy body disease, Parkinson’s disease, prion disease, and vascular disease. The greatest risk factor for developing dementia is age. The prevalence of dementia is 1%-2% at age 65 and 30% at age 85 (APA, 2013). Dementia has been identified in over 45% of older adults presenting at emergency departments (Kiliçaslan et al., 2022). Alzheimer’s disease is the most common type of dementia and comprises 60%-90% of dementia (APA, 2013; Silva et al., 2021). The worldwide cost of dementia is more than $800 billion per year. The average individual cost ranges from $30,000 to $100,000 per year, with an average cost of almost $50,000 per year (Cacabelos et al., 2022).

Dementia generally has an insidious onset, gradual progression, and, over time, causes severe deficits in functional ability. Dementia influences two or more cognitive domains: complex attention, executive function, language, learning and memory, perceptual motor, and social cognition (APA, 2013). The components and symptoms of each of the six cognitive domains are discussed below.

Complex attention components are sustained, divided, and selected attention and processing speed. The symptoms are difficulty in places with multiple stimuli, being easily distracted, being unable to attend to and process new information, experiencing delayed processing of information and thoughts, and requiring tasks to be broken down into individual steps.

The components of executive function are planning, decision-making, working memory, and mental flexibility. The symptoms are unable to complete multi-step tasks and they need assistance with making decisions.

Expressive and receptive language are the components of the language cognitive domain. The symptoms are using general phrases (e.g., “that thing”), using general pronouns instead of names, not recalling family members’ and friends’ names, grammatical errors, echolalia (automatic repetition of things other people said), automatic speech, and mutism.

Learning and memory components are immediate, recent, and long-term memory. The symptoms are repetitive, unable to recall short lists of items, and requiring frequent reminders in order to complete routine tasks.

Visual perception, visual construction, perceptual-motor, and praxis are the components of the perceptual-motor cognitive domain. The symptoms are difficulty conceptualizing, planning, organizing, and sequencing movements to carry out previously routine activities, such as cooking and driving; trouble navigating familiar surroundings; and confusion in situations with lower levels of light.

The components of social cognition are recognition of emotion and understanding of social behavior. The symptoms are making decisions without regard to safety, inappropriate social behavior (e.g., inappropriate sexual behavior), and lack of awareness or understanding of feedback from others.

The Mini-Mental State Examination (MMSE) is the gold standard instrument used to assess the level of cognitive ability in older adults. The Clock Drawing Test and Quick Confusion Scale (QCS) are also valid and reliable measures (Irons et al., 2002; Kiliçaslan et al., 2022; Mukherjee et al., 2023). Instruments used to assess dementia are presented in Table 2.

The DSM-V uses the term neurocognitive disorder instead of dementia when diagnosing degenerative cognitive conditions that primarily influence older adults. Neurocognitive disorders are categorized as major or mild, and dementias are classified as major neurocognitive disorders. When diagnosing a major neurocognitive disorder, the subtype is identified as Alzheimer’s disease, frontotemporal lobar degeneration, human immunodeficiency virus (HIV) infection, Huntington’s disease, Lewy body disease, Parkinson’s disease, prion disease, vascular disease, multiple etiologies, or unspecified. Major neurocognitive disorders are also categorized by the presence or absence of behavioral disturbance and level of severity (mild, moderate, or severe). Cognitive deficits must not be exclusively associated with delirium or better explained by another mental disorder (APA, 2013).

Major neurocognitive disorders are characterized by a significant cognitive decline from a previous level of performance in at least one of the following domains: complex attention, executive function, language, learning and memory, perceptual-motor, or social cognition. The cognitive decline is identified by the individual, knowledgeable informant, or clinician and is documented by neuropsychological testing or quantified cognitive assessment. The cognitive deficits and decline must interfere with daily functioning, specifically instrumental activities of daily living (IADLs) or activities of daily living (ADLs) (APA, 2013). IADLs and ADLs are listed in below.

IADLs

• Housecleaning and home maintenance
• Managing communication
• Managing finances
• Managing medications
• Shopping and meal preparation
• Transportation and shopping

ADLs

• Ambulating, transferring, and positioning
• Continence
• Dressing
• Feeding
• Personal hygiene
• Toileting (Edemekong et al., 2023)

Determination of the appropriate subtype of major neurocognitive disorders enables clinicians to establish the most appropriate treatment plan. Each subtype is discussed below.

Major Neurocognitive Disorder Due to Alzheimer’s Disease

Alzheimer’s disease is characterized by an insidious onset, gradual progression, and impairment in two cognitive domains (complex attention, executive function, language, learning and memory, perceptual motor, and social cognition). Alzheimer’s disease is probable if genetic testing or family history is positive or if evidence of learning and memory and at least one other cognitive domain impairment is present, and the course of cognitive decline is gradual, steady, and progressive. Often, behavioral and psychological symptoms, such as irritability, agitation, and wandering, are present and create distress, especially for caregivers (APA, 2013).

The mean duration of survival after a diagnosis of Alzheimer’s disease is approximately ten years; however, some individuals may live up to 20 years after diagnosis. Memory loss develops early in the progression of Alzheimer’s disease and adversely influences the ability to function independently, but social functioning and procedural memory are retained for a longer time. In late-stage Alzheimer’s disease, people experience incontinence, gait disturbance, and dysphagia. Diagnosis may be confirmed by post-mortem histological examination and will reveal cortical atrophy, amyloid-predominant neuritic plaques, and tau-predominant neurofibrillary tangles in the brain (APA, 2013; Cummings, 2021; Silva et al., 2021).

Major Neurocognitive Disorder Due to Frontotemporal Lobar Degeneration 

Frontotemporal dementia is characterized by an insidious onset, gradual progression, and either a behavioral or a language variant. Frontotemporal dementia with a behavioral variant requires a significant decline in the social cognition domain and the executive functioning domain and at least three of the following behavioral symptoms: disinhibition, apathy or inertia, loss of empathy; perseverative or ritualistic behavior, or hyper-focus on oral functions and dietary changes.

Individuals with frontotemporal dementia with a language variant often have progressive aphasia. Diagnosis of a language variant requires a significant decrease in language ability, as evidenced by the amount of speech production and deficits in the selection of accurate words, grammar, or comprehension. The learning memory and perceptual motor cognitive domains are retained for a longer time. Frontotemporal dementia is probable if genetic testing or family history is positive or if neuroimaging identifies frontal and temporal atrophy. Extrapyramidal symptoms, muscle atrophy or weakness, and visual hallucinations may sometimes be present (APA, 2013).

Approximately 5% of dementia is frontotemporal. The mean duration of survival is 6 to 11 years after symptoms start and 3 to 4 years after a diagnosis is made. Frontotemporal dementia often occurs when an individual is in their early 60s and may result in legal, work, and family problems due to disruptive, disinhibited behavior (APA, 2013).

Major Neurocognitive Disorder Due to HIV Infection

HIV dementia is diagnosed when individuals have cognitive impairment and HIV infection with no other medical or psychiatric condition that better explains their cognitive decline. Primary features include problematic complex attention and executive function. Emotional lability, aggression, and apathy may also be present. The course of HIV dementia is often variable and may include improvement, progression, or fluctuations. Less than 5% of individuals with HIV experience major neurocognitive disorders due to HIV infection (APA, 2013).

Major Neurocognitive Disorder Due to Huntington’s Disease

Insidious onset and progressive cognitive impairment are inherent components of Huntington’s disease. Executive functioning declines early in the course of Huntington’s disease, and learning and memory are preserved for a longer time. Cognitive and behavioral changes precede the slowing of voluntary movement and choreiform movements that are characteristic of Huntington’s disease. Diagnosis is based on the presence of these extrapyramidal motor abnormalities and a family history of Huntington’s disease or genetic testing. Associated symptoms include apathy, anxiety, depression, irritability, obsessive-compulsive behaviors, disinhibition, and impulsivity. The average age of diagnosis is 40 years, with progressive deterioration and death approximately 15 years after diagnosis. In the late-stage Huntington’s disease, motor impairment and inability to swallow become profound (APA, 2013).

Major Neurocognitive Disorder Due to Lewy Body Disease

Insidious onset and gradual progression characterize Lewy body dementia. Individuals with Lewy body dementia may display two or more of the following symptoms: 1) fluctuating cognition, attention, and alertness; 2) recurrent detailed visual hallucinations; and 3) cognitive declines followed by sudden Parkinsonian symptoms, or they may display at least one of these symptoms along with either rapid eye movement, sleep disorder, or severe neuroleptic sensitivity, including neuroleptic malignant syndrome (altered mental status, fever, and muscle rigidity).  Typically, complex attention and executive function decline are early symptoms, and sudden Parkinsonian symptoms develop at least a year later. Behavioral disturbances, auditory hallucinations, delusions, depression, repeated falls, unexplained loss of consciousness, and orthostatic hypotension may also be present. Although potentially helpful in treating hallucinations and other psychotic symptoms, antipsychotic medications with neuroleptic components should be avoided in individuals with Lewy body dementia (APA, 2013; Hershe & Coleman-Jackson, 2019).

Approximately 2% to 30% of dementia are thought to be Lewy body dementia. The male-to-female ratio for Lewy body dementia is 1.5 to 1. The mean duration of survival is 5 to 7 years. Lewy body dementia may occur after the age of 60 but most commonly develops in the mid-70s, with a median age of 76.3 years. Quality of life tends to be extremely low in large part because of visual hallucinations, motor impairment, and sleep problems. Individuals with Alzheimer’s and vascular dementia often also have concurrent Lewy body pathology, which explains the variability in presentation and clinical course (APA, 2013; Hershe & Coleman-Jackson, 2019).

Major Neurocognitive Disorder Due to Parkinson’s Disease

Up to 75% of individuals who have been diagnosed with Parkinson’s disease will experience an insidious onset and gradually progressing cognitive impairment. Associated symptoms include apathy, depression, anxiety, hallucinations, delusions, personality change, rapid eye movement, sleep disorder, and sleepiness during the day. Parkison’s disease occurs more frequently in men than in women and most commonly presents when a person is in their early 60s. Parkinson’s dementia may co-occur with Alzheimer’s disease and vascular dementia (APA, 2013).

Major Neurocognitive Disorder Due to Prion Disease

An insidious onset characterizes prion disease, rapid progression; biomarker evidence of prion disease or symptoms of prion disease, such as myoclonus or ataxia; and dementia that is not better explained by another medical or psychiatric condition. Prion disease is associated with a group of sub-acute spongiform encephalopathies, with Creutzfeldt-Jacob disease as the most common. Symptoms include cognitive impairment, ataxia, chorea, myoclonus, dystonia, and an increased startle reflex. Magnetic resonance imaging shows multifocal gray matter hyperintensities in cortical and subcortical brain regions (APA, 2013).

The peak age of developing prion disease is 67 years. Prodromal symptoms, such as fatigue, anxiety, appetite issues, sleeping issues, and decreased concentration, may precede altered vision, incoordination, abnormal movements, and rapidly progressing dementia. Typically, severe symptoms that interfere with daily functioning and quality of life develop over 3 to 6 months (APA, 2013).

Major Neurocognitive Disorder Due to Vascular Disease

Vascular dementia is characterized by an insidious onset, gradual progression, and cerebrovascular disease or decline in the cognitive domains of complex attention and executive function. Vascular dementia is probable if neuroimaging shows parenchymal injury associated with cerebrovascular disease, symptoms are associated with cerebrovascular events, or clinical and genetic evidence supports the presence of cerebrovascular disease. Vascular lesions may occur in tiny or large vessels and may be localized or diffuse. A stair-step presentation, with cognitive declines and plateaus, may mirror the occurrence of cerebrovascular events. Abulia (lack of initiative), depression, emotional lability, and psychomotor slowing may also be present (APA, 2013).

Vascular dementia is the second most common type of dementia after Alzheimer’s disease. Approximately 16% of people 80 years and above have vascular dementia, and within three months after experiencing a stroke, 20% to 30% of individuals are diagnosed with vascular dementia. Vascular dementia and Alzheimer’s disease frequently occur together (APA, 2013).

Pharmacological treatment differs depending on the type of dementia. For Alzheimer’s disease, the most prevalent form of dementia, two types of pharmacological treatment are 1) acetylcholinesterase inhibitors, which increase acetylcholine availability and decrease the effects of cholinergic loss, and 2) an N methyl-D-aspartate receptor antagonist, which inhibits glutamate-mediated excitotoxicity (Cummings, 2021; Silva et al., 2021). Medications to treat Alzheimer’s disease are listed below.

Acetylcholinesterase Inhibitors (for Mild to Moderate Alzheimer’s Disease)

Donepezil (Aricept®) 10 mg by mouth daily

Rivastigmine (Exelon®) 3 mg or 6 mg by mouth BID

Galantamine (Razadyne®) 8 mg or 12 mg by mouth BID

N-methyl-D-aspartate Receptor Antagonist (for Moderate to Severe Alzheimer’s Disease)

Memantine (Namenda®) 10 mg by mouth BID (Cummings, 2021; Silva et al., 2021)

These medications may need to be titrated. They may come in alternative forms like extended-release or patch.

The use of Food and Drug Administration-approved medications and alternative and complementary treatments, such as vitamins and supplements, using nano-based formulations is being investigated. Nanoparticles are colloidal systems with a size of less than 1μm used to deliver pharmacological agents and are classified as hybrids, inorganic, and organic. Nanostructures are thought to be safe ways to deliver substances that target specific areas in the nervous system using lower doses than traditional delivery systems (Karthika et al., 2022; Silva et al., 2021). Recently, the Food and Drug Administration has approved Brexpiprazole (Rexulti®) for the treatment of agitation in Alzheimer’s disease. Clinical trials are underway for additional medications to treat neuropsychiatric symptoms, such as agitation, apathy, and psychosis (Cummings, 2021).

Nonpharmacological intervention for dementia involves the affected individual and their family. Creation and maintenance of a safe and supportive environment and provision of anticipatory guidance, information, and resources are critical to maximizing quality of life. Providing consistency; verbal, visual, and physical cues; meaningful photographs and items; daily regular exercise, including range of motion; healthy, readily available food and beverage options; routine toileting; consistent bedtime rituals; and wearable identification will help promote quality of life and functional ability (Ravuri & Parthasarathi, 2019).

Individuals with a first-degree relative with major depressive disorder are much more likely to have depression (APA, 2013). This affective condition occurs in older women more commonly than in older men (Cacabelos et al., 2022). Depression has been identified in over 35% of the older adults presenting at emergency departments. Approximately 45% of hospitalized older adults with depression display psychotic features. This disorder may coexist with dementia and increases the risk of delirium. Depression is associated with higher morbidity and mortality rates and increased healthcare utilization (Baba et al., 2022; Kiliçaslan et al., 2022). Although mortality is high, approximately 80% of individuals with major depressive disorder recover (APA, 2013).

Sad feelings and depressed moods are normal emotions that nearly everyone experiences and are associated with loss, uncertainty, and disappointment. When depressive symptoms persist, interfere with functioning or quality of life, or are associated with suicidal thoughts, these symptoms need to be identified and treated. Older adults with depression often manifest with agitation, hypochondriasis, and somatic symptoms, which can complicate diagnosis. Depression can be categorized as major depressive disorder or persistent depressive disorder (APA, 2013; Baba et al., 2022).

The Hamilton Depression Rating Scale (HDRS) is the gold standard instrument used to assess older adults for Depression. The Geriatric Depression Scale and Beck Depression Inventory are also valid and reliable measures (Yesavage et al., 1982; Beck et al., 1988). Instruments used to assess depression are presented in below.

Beck Depression Inventory is a 21-item self-rated scale. The scoring is:

>40: Extreme depression
31-40: Severe depression
21-30: Moderate depression
17-20: Mild depression
11-16: Some depression
0-10: No depression

Geriatric Depression Scale (GDS) is a 30-item self-rated scale The scoring is:

21-30: Moderate to severe depression
11-20: Mild depression
0-10: No depression

Hamilton Depression Rating Scale (HDRS) is the Gold-standard of depression assessment scales. It is a 17-item observer-rated measure. The scoring is:

Score of > 18: Severe depression
Score of 14-17: Moderate depression
Score of 10-13: Mild depression
Score of 0-9: No depression (Beck et al. 1988; Hamilton, 1960; Yesavage et al., 1982)

Major depressive disorder is characterized by symptoms occurring nearly every day for at least two weeks that represent a change from baseline. Depressed mood or inability to feel pleasure (anhedonia) must be present along with four or more of the following symptoms: weight loss or gain along with decreased or increased appetite; insomnia or hypersomnia; psychomotor agitation or retardation; fatigue or decreased energy; feeling worthless or guilty; decreased ability to think, concentrate, or make decisions; or thoughts of death, suicidal ideation, or suicide attempt. Individuals with major depressive disorder may be distracted and have significant memory impairment. Associated symptoms may include anxiety, irritability, and somatic concerns. Symptoms impair social and occupational functioning as well as other important functional areas of life. Symptoms are not attributable to a medical condition, substance use, or other mental disorders (PA, 2013).

Major depressive disorder may be a single episode or recurrent. Specifications that should be included in the diagnosis are severity, presence or absence of psychotic features, and other features, such as anxious distress, melancholic features, and atypical features (APA, 2013). Persons with co-occurring medical illnesses are more likely to experience pain and functional impairment than those who do not have co-occurring medical illnesses. Substance use and other mental health conditions often occur concomitantly. When symptoms occur for two years or more, the diagnoses are listed as persistent depressive disorder and major depressive disorder (APA, 2013; Dening & Aldridge, 2021).

Pharmacological treatment of depression includes the following categories of medications (Baba et al., 2022).

1. Selective serotonin reuptake inhibitors (SSRIs) – SSRIs are the first line of treatment for depression and include Citalopram (Celexa®), Escitalopram (Lexapro®), Sertraline (Zoloft®), Fluoxetine (Prozac®), Paroxetine (Paxil®), and Vilazodone (Viibryd®).
2. Serotonin-norepinephrine reuptake inhibitors (SNRIs) – SNRIs are typically considered the second line of treatment for depression and include Duloxetine (Cymbalta®), Venlafaxine (Effexor®), Desvenlafaxine (Pristiq®), and Levomilnacipran (Fetzima®).
3. Atypical antidepressants – Atypical antidepressants are the third line of treatment for depression or may serve as an adjunct to a first- or second-line antidepressant and include Bupropion (Wellbutrin®), Mirtazapine (Remeron®), Trazodone (Desyrel®), Nefazodone (Serzone®), and Vortioxetine (Trintellix®).
4. Tricyclic antidepressants (TCAs) – TCAs are considered the fourth line of treatment for depression and include Amitriptyline (Elavil®), Imipramine (Tofranil®), Nortriptyline (Pamelor®), Doxepin (Silenor®), Trimipramine (Surmontil®), Desipramine (Norpramin®), and Protriptyline (Vivactil®). TCAs tend to be lethal when an overdose is taken, are associated with cardiac and electrocardiogram changes, and cause a number of adverse effects, such as orthostatic hypotension, dry mouth, blurry vision, weight gain, and drowsiness.
5. Monoamine oxidase inhibitors (MAOIs) – MAOIs are considered the fifth line of treatment for depression and include Tranylcypromine (Parnate), Phenelzine (Nardil), and Isocarboxazid (Marplan). MAOIs tend to be effective but often cause adverse effects and untoward interactions with other medications. To prevent a hypertensive crisis, individuals taking MAOIs need to avoid food and beverages containing tyramine, such as pickled or smoked fish, sauerkraut, matured cheeses, and homemade wine. To prevent serotonin syndrome, a life-threatening condition, MOAIs should not be taken with SSRIs.
6. Other psychiatric medications – Antipsychotic and mood stabilizing medications may be used in conjunction with antidepressants to enhance the effects of antidepressants, treat psychotic depression, or help control anger and irritability.

Psychotherapy, such as cognitive behavioral, solution-focused, and interpersonal therapy, should occur prior to beginning antidepressants or in conjunction with pharmacological management (Lind et al., 2022). Ensuring that the older adult has a healthy, balanced diet, routine exercise, and adequate sleep is essential in the treatment of depression. Additionally, bright light, aroma, music, and other therapies may serve as useful adjunctive treatments. Older adults with refractory depression who have not responded to psychopharmacological management may be treated with electroconvulsive therapy or transcranial magnetic stimulation (Baba et al., 2022).