September/October 2018

Psychopharmacology for Geriatricians: Antidepressants & Antianxiety Medications
By Jamshid A. Marvasti, MD, and Joseph Secor-Taddia, DO, MSc
Today's Geriatric Medicine
Vol. 11 No. 5 P. 20

Antidepressant drugs are used in the treatment of a variety of psychiatric disorders including major depressive disorder, generalized anxiety disorder, posttraumatic stress disorder, panic disorder, obsessive-compulsive disorder (OCD), bulimia nervosa, and premenstrual dysphoric disorder. Additionally, select antidepressants have been approved for the management of neuropathic pain and fibromyalgia, smoking cessation, and ADHD.

Although these two classes of medications were introduced to the market for depression and anxiety disorders, clinicians have determined that patients suffering from nonpsychiatric disorders have found relief using these medications. Examples include antidepressants used for chronic pain and tranquilizers used for muscle spasms. Furthermore, physicians are using antidepressants in off-label treatment of vasomotor symptoms of menopause, migraine prophylaxis, and treatment of premature ejaculation.1

Because statistics reveal that more antidepressants and antianxiety/antihypnotic medications are prescribed by primary care physicians than by psychiatrists, it's important that all clinicians are familiar with the indications for these drugs, their side effects, and their unique effects in older adults.

Recurrent episodes of psychiatric disorders (depression, psychosis, mania) have a detrimental effect on the brain.2 These negative effects include neurodegeneration associated with neurotoxicity due to inflammation, reactive oxygen and nitrogen species, and apoptosis (death of cells). From a positive point of view, psychiatric medications (antidepressants, mood stabilizers, atypical antipsychotics) have neuroprotective effects, including increasing neurogenesis and preventing apoptosis.

Research indicates that dietary supplements with antioxidant activity enhance the neuroprotective effects of these medications. These adjuvant therapies included omega-3 fatty acids, N-acetylcysteine, vitamin D, nicotine, melatonin, erythropoietin, and caffeine.2

Response to Medications Among Geriatric Patients
The peripheral and central anticholinergic side effects of antidepressants include constipation, urinary retention, delirium, and cognitive dysfunction. Both the antihistiminergic side effects (sedation) and antiadrenergic side effects (postural hypotension) can increase the risk of fall.3

Geriatric patients are more susceptible to the adverse effects of medications due to the physiology of aging. Decreased cardiac output, reduced liver size, and diminished glomerular filtration rate lead to decreased drug metabolism and clearance. Special consideration should be given when prescribing antidepressants to the elderly to avoid exacerbating any preexisting medical conditions and optimize treatment outcomes. In addition to detailed history-taking, periodic follow-up and special testing (metabolic, hepatic, and renal function) should be performed to ensure patient safety. EKGs should be performed periodically to rule out any new or worsening cardiac problems such as prolonged QTc, arrhythmias, and sudden death.

Common Medical Disorders That May Cause Depression
The clinical literature reports a number of medical diseases that may cause depression and other mood disorders. These include hypothyroidism, Cushing's disease, Addison's disease, Alzheimer's disease, diabetes mellitus, Parkinson's disease, anemia, obstructive sleep apnea, congestive heart failure, multiple sclerosis (MS), Lyme disease, rheumatoid arthritis, restless leg syndrome, systemic lupus erythematosus, ulcerative colitis, and chronic infections such as mononucleosis and tuberculosis.

In these cases, clinicians should treat the causes of depression, ie, the underlying medical problem(s). If the depression persists, antidepressants may be used. In subclinical hypothyroidism, depression is usually present along with a high-normal thyroid-stimulating hormone level, but normal T3 and T4 levels. The literature strongly suggests that these patients benefit from additional thyroid hormone, especially if they had a poor response to antidepressants.4,5

Conversely, clinicians should be aware that psychiatric disorders may mimic general medical illnesses. For example. patients with hyperventilation syndrome due to anxiety may complain of shortness of breath, weakness, paresthesia, headache, and carpopedal spasm.1

Medications That May Cause Depression
Antihypertensive medications such as Serpasil (reserpine), Inderal (propranolol), Aldomet (methyldopa), Catapres (clonidine), and hydralazine may cause or increase depressive symptoms.

Corticosteroids and other hormones, such as estrogen and progesterone, oral contraceptive pills, antiparkinsonian drugs such as Sinemet (carbidopa/levodopa) and amantadine, anxiolytics such as Valium (diazepam), antiviral medications such as interferon and ribavirin, prokinetic agents such as Reglan (metoclopramide), and dermatological medications such as isotretinoin (vitamin A derivative) may also contribute to depression.

It is well known that alcohol and other substances of abuse also contribute to mood disorders.5 Clinicians should be familiar with medications that may cause psychological problems. If such problems arise, clinicians may identify alternative medications. If depression persists, antidepressants may be used.

General Considerations About Side Effects
The side effects of antidepressants and antianxiety medications range from temporary and relatively mild (dry mouth) to long-term (metabolic disorder) and even life-threatening disorders (serotonin syndrome). It's important to perform a detailed history and physical exam, making sure to obtain details of past medications prior to starting pharmacotherapy.

Many patients stop taking their medication due to side effects, so it's important to inform them of these risks while also encouraging them to take their medication as prescribed so they can improve. Some patients can convince themselves they're experiencing side effects when they're actually not, while others may be too shy or embarrassed to discuss the side effects with their doctors. For example, if patients develop diplopia after starting a selective serotonin reuptake inhibitor (SSRI), they may learn to cover one eye with their hair in order to have single vision. Some psychiatric medications may cause vocal tics (grunting, coughing, or throat clearing) or motor tics (eye blinking, facial grimaces, or shoulder shrugging).6

Clinicians must know how to identify all possible side effects of a medication and be able to educate patients. Patients must be informed about side effects, information that hospitals, clinicians, and pharmacies have readily available. Clinicians should clarify to patients and their caregivers the potential side effects and provide them with hard copies of relevant information.

Antidepressant Medications
SSRIs are a specific class of antidepressant medications that are particularly safe and effective, contributing to their widespread use in the field of psychiatry as first-line agents in the treatment of depression and anxiety. SSRIs are also used in the off-label treatment of agitation in dementia, impulse control disorder, and borderline personality disorder.1

Choosing Antidepressant Medications
Some important factors to consider when choosing the optimal antidepressant are the lethal capacity in overdose, the patient's presenting symptoms and working diagnosis, and the medication's side effects. Obviously, patients who are suicidal should probably not be taking tricyclic antidepressant (TCA) medications such as Elavil (amitriptyline) or Tofranil (imipramine). It's not difficult to overdose on these medications since one week's prescription can be fatal if taken all at once.

In regard to presenting symptoms, for a depressed patient with panic attacks or premenstrual symptoms, the medication of choice may be an SSRI such as Prozac (fluoxetine), which may be effective in treating all three disorders.7

Patients with diagnosed bipolar or psychotic disorders are more vulnerable to the activating effects that SSRIs have on the central nervous system (CNS). Approach these patients with caution, since treating their mood symptoms with an SSRI can push them into full-blown mania or psychosis. Those with a history of seizure, stroke, or head trauma are more safely treated with an SSRI or Effexor (venlafaxine) than with TCAs or Wellbutrin (bupropion). Depressed individuals with OCD, anxiety, rumination, and irritability may respond to SSRIs rather than non-SSRI medications.1

Those with chronic physical pain syndromes and depression may benefit from Elavil or Cymbalta (duloxetine), which are both effective in treating depression and physical pain. For those who are obese and depressed, Wellbutrin may be used if they are concerned about their weight. SSRIs may also help with weight loss, but certain antidepressants such as Remeron (mirtazapine) should be avoided in obese patients to limit further weight gain. Remeron is a good treatment option to use in patients with eating disorders such as anorexia nervosa to increase their weight.1

For those who have coexisting sleep disorders, Remeron may be indicated at night as it is sedating. Sometimes TCA medications are prescribed, eg, Elavil or Sinequan (doxepin) because their antihistiminergic side effect profile causes sedation. If a patient has symptoms of depression in addition to low energy, anhedonia, and apathy, a dopamine/noradrenergic reuptake inhibitor such as Wellbutrin might be beneficial due to its activating effects on the CNS. Wellbutrin should not be prescribed to individuals with epilepsy or other conditions that lower the seizure threshold, such as anorexia nervosa, bulimia nervosa, active brain tumors, and concurrent alcohol and/or benzodiazepine (BZD) use and/or withdrawal.1

Side Effects of SSRI Medications
Some notable side effects of SSRIs such as Prozac, Zoloft (sertraline), and Lexapro (escitalopram) are nightmares, diplopia, amnesia, dilated pupils, dry eyes, light intolerability, diaphoresis, tinnitus, hypersalivation, sexual dysfunction, and constant yawning.8

Additional effects include gastrointestinal disturbances such as nausea, vomiting, and diarrhea. CNS disturbances include headache, insomnia, sedation, agitation, tremors, and dizziness. More serious side effects that have occurred in patients taking SSRIs are seizures, suicidal ideation, mania, and serotonin syndrome, although these rarely occur.

The combination of SSRIs with other serotonergic drugs can precipitate serotonin syndrome, which is characterized by extreme restlessness, fever, jerking movements of muscle, hyperreflexia, agitation, muscle spasms, nausea, vomiting, diarrhea, severe low blood pressure, palpitations, and, sometimes, seizures.1 Significant hyponatremia resulting from the syndrome of inappropriate antidiuretic hormone secretion is a potentially dangerous adverse effect that's observed almost exclusively in older adults and typically during the first couple of weeks of treatment.3

SSRIs, as well as other serotonergic drugs, may directly affect platelet activation and are associated with an increase in the risk of cerebral, gastrointestinal, and postsurgical bleeding. They act synergistically with other medications that increase the risk of bleeding, such as NSAIDs, low-dose aspirin, and warfarin. The risk of falls and hip fracture does not differ among different classes of antidepressants but there's concern that chronic use of serotonergic drugs may contribute to the risk of fractures through their direct effects on bone metabolism.3

Withdrawal Symptoms of SSRI Medications
When abruptly stopped, SSRIs may cause withdrawal symptoms that may resemble the flu, with a peculiar sensation described as "electrical shocks" that go through the head or the limbs. Because it remains in the body for two weeks and gradually decreases day by day, Prozac is the only SSRI that may not produce withdrawal symptoms.

As a result of withdrawal symptoms often being misdiagnosed as a return of depression or anxiety, a mnemonic device has been created to improve detection of SSRI withdrawal symptoms. Clinicians are advised to watch for symptoms of HANGMAN: H stands for headache, A for anxiety, N for nausea, G for gait instability, M for malaise, A for asthenia (fatigue), and N for numbness (paresthesia).9

Medications for Anxiety Disorder
Clinical literature states that before speculating about any psychological etiology for anxiety, it's necessary to rule out medical conditions or behaviors known to cause anxiety. These include the following:

• Cardiopulmonary disorders: mitral valve prolapse, arteriosclerotic heart, paroxysmal tachycardia, hypoxemia, asthma, COPD, and pulmonary embolism.

• Endocrine and metabolic disorders: hypoglycemia, thyroid dysfunction, hypocalcemia, porphyria, premenstrual syndrome, and Cushing's syndrome.

• Tumors: adrenal, insulinoma, and carcinoid.

• Neurologic diseases: postconcussion syndrome, MS, temporal lobe epilepsy, Meniere's disease in earlier states, akathisia (restless leg syndrome) delirium, and dementia.

• Substance-related disorders: withdrawal from alcohol, tranquilizer, hypnotics, nicotine, and caffeine.

• Over-the-counter, prescription, or illicit drug use: amphetamines, appetite suppressants, asthma medications, coffee, nasal decongestants, steroids, and street drugs such as cocaine.1,5

Antianxiety medications are used for the treatment of generalized anxiety disorder, panic disorder, stress-related tension, social phobia/anxiety, and insomnia. BZDs have been effective on a short-term basis; however, the issue of developing tolerance and dependency—and eventually addiction and abuse—has been a barrier to prescribing for longer periods.

Also, BZDs can cause depression in some individuals. Valium, Xanax (alprazolam), Klonopin (clonazepam), and Ativan (lorazepam) are the most frequently prescribed BZDs. Klonopin and Valium are long-acting while Xanax and Ativan are short-acting. Many clinicians are using SSRIs, Buspar (buspirone), Atarax (hydroxyzine), and beta-blockers to treat anxiety because they are effective and not habit-forming (do not cause addiction or dependency).10

Antianxiety Medications for Geriatric Populations
Anxiolytic sedative-hypnotic medications should be used carefully with older adults. The SSRIs and selective serotonin-norepinephrine reuptake inhibitors have replaced BZDs as the first-line treatment for anxiety in the geriatric population. Even a single small dose of Valium or Restoril (temazepam) may cause memory impairment and psychomotor disturbances in older adults. BZDs have also been linked to adverse respiratory outcomes in geriatric patients with COPD and may increase the risk for Alzheimer's dementia.3

Although BZD receptor agonists such as Lunesta (eszopiclone), Sonata (zaleplon), and Ambien (zolpidem) are considered safer than BZDs, they are still associated with cases of falls and hip fractures, cognitive impairment, and traffic accidents in older individuals. Both BZDs and BZD receptor agonists are associated with increased risk of mortality in older patients. Relative contraindications include sleep apnea and/or prescription opioid use due to diminished respiratory drive and dementia due to increased risk of confusion.3

Notable side effects of BZDs include sedation, fatigue, depression, dizziness, ataxia, slurred speech, weakness, forgetfulness, confusion, hyperexcitability, and nervousness. More serious side effects are respiratory depression, especially when taken with CNS depressants (prescription opioids, narcotics, and alcohol), and overdose. Concomitant use of BZD and opioids medications is a serious risk that may result in profound sedation, respiratory depression, coma, and death. Rarely have there been cases of hepatic dysfunction, renal dysfunction, and blood dyscrasias reported in patients taking BZDs.11

Clinical literature indicates that abruptly discontinuing BZDs in individuals who have been taking them daily for longer than one month will cause withdrawal (abstinence syndrome). Withdrawal symptoms typically last up to 10 days following moderate usage; however, some patients may have prolonged attenuated withdrawal symptoms lasting for months. The possibility of seizures needs to be considered if higher doses of short-acting BZD are abruptly discontinued.

Clinicians should be aware that medical disorders may cause depression and anxiety and understand that it's wise to first diagnose the underlying medical problems. It may be appropriate to treat both the underlying medical problems and the psychiatric presentation simultaneously.

Moreover, depression and anxiety occasionally may mimic physiological disorders. In these cases, clinicians should not ignore the psychiatric disorder that's causing the somatic presentation. Lastly, clinicians should be aware of potential side effects of psychiatric medications and communicate these clearly to patients. It's important as well to discuss these with caregivers, given that some geriatric patients may suffer from memory or attention span disorders.

At the heart of this matter are clinicians' relationships with their patients and the need for a deeper understanding of the patients' psychosocial behavior. In other words, it's not merely the medication but the hand that is prescribing it that determines the extent to which the treatment will be successful.

— Jamshid A. Marvasti, MD, is a psychiatrist at Prospect Manchester Hospital in Manchester, Connecticut. An assistant clinical professor at the University of New England College of Osteopathic Medicine, he's published articles and edited books including War Trauma in Veterans and Their Families (2012) and Psycho-Political Aspects of Suicide Warriors, Terrorism, and Martyrdom (2008). Marvasti may be reached at jmarvasti@aol.com.

— Joseph Secor-Taddia, DO, MSc, is a recent graduate of the University of New England College of Osteopathic Medicine and will be attending a psychiatry residency program in the 2019 residency program match. Correspondence concerning this article should be addressed to Joseph Secor-Taddia, 11 Hills Beach Rd, Decary Hall Rm 34, Biddeford, ME 04005. E-mail: jsecortaddia@une.edu.

References
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4. Cohen BM, Sommer BR, Vuckovic A. Antidepressant-resistant depression in patients with comorbid subclinical hypothyroidism or high-normal TSH levels. Am J Psychiatry. 2018;175(7):598-604.

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6. Marvasti JA, Wu P, Merritt R. Psychopharmacology for play therapists. Int J Play Ther. 2018;27(1):35-45.

7. Sequenced Treatment Alternatives to Relieve Depression (STAR*D) Study. National Institute of Mental Health website. https://www.nimh.nih.gov/funding/clinical-research/practical/stard/index.
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8. Silverman HM. The Pill Book. 15th ed. New York, NY: Bantam Books; 2012:1048-1198.

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11. Stahl SM. Stahl's Essential Psychopharmacology Prescriber's Guide. 5th ed. New York, NY: Cambridge University Press; 2014.