Depression and Anxiety:
Drugs are frequently used to treat depression and anxiety. The major classes of drugs include selective serotonin reuptake inhibitors (SSRIs), serotonin and norepinephrine reuptake inhibitors (SNRIs), monoamine oxidase inhibitors (MAOIs), tricyclic antidepressants (TCAs) and other agents.
Serotonin reuptake inhibitors:
Serotonin reuptake inhibitors (SSRIs) are first-line agents for depression and work by increasing the amount of the neurotransmitter serotonin in the brain. They are first-line treatment options primarily because of their safety profile, efficacy, and limited drug-to-drug interactions.
Fluoxetine (Prozac) is dosed at 20 mg in the morning and may increase to 80 mg daily. Each titration must occur after a few weeks on the drug. It is not indicated for those less than eight years old. Fluoxetine has a long half-life and is less likely to lead to withdrawal symptoms if abruptly discontinued. A weekly formulation is available that is dosed 90 mg once a week.
Fluoxetine can increase warfarin, phenytoin, carbamazepine, TCAs, and benzodiazepines. It may lower the therapeutic effect of codeine. It may cause serotonin syndrome when combined with other SSRIs and other antidepressants.
Sertraline (Zoloft) is started at 25-50 mg orally daily, and the dose can be increased gradually to a maximum of 200 mg daily. It is not indicated for those less than six years old. Common side effects include dizziness, fatigue, headache, insomnia, somnolence, diarrhea, nausea, tremor, and diaphoresis. It may interact with warfarin, cimetidine, digoxin, and diazepam. It is indicated for major depressive disorder, premenstrual dysphoric disorder, panic disorder, posttraumatic stress disorder (PTSD), obsessive-compulsive disorder (OCD), and social anxiety disorder.
Paroxetine (Paxil) has a short half-life and may lead to discontinuation syndrome when the drug is stopped or missed doses. It has the most potent anticholinergic effects of any of the SSRIs. For major depression, the standard form is dosed 10 mg per day to a maximum of 50 mg orally per day, and the extended-release form (Paxil CR) is dosed at 12.5 mg once a day to a maximum of 62.5 mg orally every day. Paroxetine is indicated for major depressive disorder, panic disorder, OCD, social anxiety disorder, generalized anxiety disorder, PTSD, and premenstrual dysphoric disorder. Side effects include somnolence, insomnia, dizziness, headache, nausea, xerostomia, constipation, diarrhea, weakness, tremor, and diaphoresis. Sexual dysfunction is most problematic with paroxetine among the SSRIs (Williams & Nieuwsma, 2020).
Citalopram (Celexa) is indicated for depression and is dosed at 20 mg once a day, and the dose can be increased to 40 mg once a day after one week. It interacts with macrolide antibiotics, cimetidine, azole antifungal, omeprazole, and carbamazepine. Side effects include sleep disturbance, xerostomia, nausea, and diaphoresis.
Escitalopram (Lexapro) is dosed at 10 mg daily and may increase to 20 mg after one week. It has few interactions but may interact with other SSRIs, cimetidine, and alcohol. The FDA warns that both citalopram (more than 40 mg/day) and escitalopram (more than 20 mg/day) can potentially prolong the QT interval and may be fatal. They should be used cautiously in those with underlying heart disease and those prone to becoming hypokalemic.
Serotonin and norepinephrine reuptake inhibitors:
Serotonin and norepinephrine reuptake inhibitors (SNRIs) are newer drugs to treat depression and anxiety. Drugs in this class include venlafaxine (Effexor), duloxetine (Cymbalta), desvenlafaxine (Pristiq), milnacipran (Savella), levomilnacipran (Fetzima). This class has a similar safety profile to SSRIs, but occasionally they may be associated with increased blood pressure. They can be used as a first-line agent to treat depression/anxiety or in those who do not respond to SSRIs. The SNRIs work on multiple neurotransmitters and do a better job of reducing the pain and other somatic complaints in depression when compared to other antidepressants (Thase, 2011).
Venlafaxine (Effexor) comes as an extended-release form and is dosed 37.5 to 75 mg a day and may be titrated up to 225 mg daily. It may interact with other antidepressants, cimetidine, diuretics, and alcohol. It should not be used in those with severe uncontrolled hypertension. At doses less than 150 mg daily, it mainly affects serotonin levels, but higher doses affect dopamine and norepinephrine levels. Discontinuation syndrome is high with this drug.
Desvenlafaxine (Pristiq) is dosed at 50 mg daily for adults. It may be titrated up to 400 mg once a day, but positive effects are not proven with higher doses (as reported by the manufacturer). Common side effects include nausea, headache, dizziness, dry mouth, insomnia, fatigue, and bowel disturbance. It may interact with other SSRIs or blood thinners.
Milnacipran (Savella) is dosed 12.5 mg daily on the first day and titrated upwards to a maximum of 200 mg daily divided every 12 hours. It should be used cautiously in those with moderate to severe renal and hepatic impairment. Those who take it may suffer from nausea, headache, dizziness, sleep disturbance, and constipation.
Levomilnacipran (Fetzima) is started at 20 mg once a day and increased to 40 mg once a day. The maximum dose is 120 mg a day. Doses should be reduced in those with moderate and severe renal insufficiency. Common side effects include nausea but may also be associated with sexual dysfunction, constipation, urinary hesitancy, and elevated heart rate.
Duloxetine (Cymbalta) is dosed at 20 mg twice a day to start and may be increased to 30 mg twice daily or 60 mg once a day in the adult. The maximum dose is 120 mg a day. It may interact with ciprofloxacin, SSRIs, TCAs, antiarrhythmic agents, and anticoagulants. Common adverse effects include nausea, headache, dry mouth, dizziness, sleep disturbance, and fatigue.
Duloxetine has multiple indications. It is approved for treating depression in addition to diabetic peripheral neuropathy, chronic musculoskeletal pain, fibromyalgia, and generalized anxiety disorder. This drug is often used by those with depression in addition to one of these co-morbid conditions.
Other antidepressants include bupropion (Wellbutrin), mirtazapine (Remeron), vortioxetine (Brintellix), vilazodone (Viibryd) and trazodone (Desyrel). Generally, this group has low toxicity in overdose and may have an advantage over the SSRIs by causing less sexual dysfunction and gastrointestinal distress.
- Bupropion is indicated for major depression, seasonal affective disorder, and smoking cessation. It is indicated for those over 17 years old. It comes in many brand names, including Wellbutrin XL, Wellbutrin SR, Aplenzin, and Forfivo XL. It increases the risk of seizures at higher doses, particularly in those with a history of seizures. Common side effects include headache, nausea, dry mouth, weight loss, dizziness, and insomnia.
- Mirtazapine (Remeron) is dosed at 15 mg at bedtime and may be increased every 1-2 weeks up to 45 mg daily in adults. It is given at bedtime because sedation is a significant side effect. Another common side effect is weight gain. Other side effects include dry mouth, constipation, and dizziness.
- Vortioxetine (Brintellix) starting dose is 10 mg daily and may be increased to 20 mg daily. The dose may be lowered to 5 mg a day for those who do not tolerate the higher dose. It works on multiple receptors and increases noradrenaline, dopamine, and glutamatergic transmission. The drug's half-life is long at approximately 57 hours, leading to a low rate of withdrawal effects. Major interactions include linezolid, other antidepressants, fentanyl, ritonavir, tramadol, and clopidogrel. Nausea is the most common side effect, but other side effects include diarrhea, constipation, dry mouth, headache, and dizziness.
- Vilazodone (Viibryd) selectively inhibits serotonin reuptake and does not work on dopamine or norepinephrine reuptake. It is dosed at 10 mg once a day for seven days, then may be titrated up to 20 mg then 40 mg once a day. This drug should be taken with food. It is commonly associated with diarrhea and nausea, and other side effects may include dizziness, dry mouth, insomnia, and fatigue. Vilazodone showed favorable effects on weight gain and possibly less sexual dysfunction than other SSRIs (Citrome, 2014).
- Trazodone is indicated for those 18 years of age and older. It is not commonly used as an antidepressant because it is very sedating.
- Educate the patient not to stop drugs abruptly
- Assess for adverse reactions
- Educate the patient on drug interactions and side effects
- When starting an antidepressant, the patient must be assessed for suicide. Suicide is more common among youths and young adults but can also affect the elderly. As the patient starts to feel better from being on the drug, some energy may return, which may increase the risk of suicide. Increased agitation, irritability, or other behavior changes may indicate a pending suicide attempt.
- The patient should be told that side effects may initially be more intense and fade over time. Patients should be encouraged to work through minor side effects until the body gets used to the drug. It may take a few weeks until symptoms start to improve, and it is important to encourage the patient to keep taking the drug.
Antipsychotics can be classified as typical (first-generation) or atypical (second-generation). Antipsychotic drugs are used to manage schizophrenia, bipolar disease, and some cases of depression.
Typical antipsychotics have existed since the 1950s and include Haloperidol (Haldol), Thioridazine (Mellaril), Molindone (Moban), Fluphenazine (Prolixin), and Perphenazine (Trilafon). Typical antipsychotics have more neurological side effects. Prescribers frequently dose antipsychotics at the EPS threshold, which is the dose that brings on minimal rigidity on the exam. This dosing method is the most effective, and higher doses are no more effective and are typically associated with poor compliance due to side effects.
Atypical antipsychotics have existed since the late 1980s. These drugs are less likely to lead to neurological side effects, which results in better compliance. This class of drugs is associated with other side effects such as weight gain, diabetes, and elevated cholesterol.
|First-generation antipsychotics||Second-generation antipsychotics|
|High Potency||Ziprasidone (Geodon®)|
|Thiothixene (Navane®)||Aripiprazole (Abilify®)|
|Fluphenazine (Prolixin®)||Risperidone (Risperdal®)|
|Perphenazine (Trilafon®)||Quetiapine (Seroquel®)|
|Haloperidol (Haldol®)||Olanzapine (Zyprexav®)|
|Low potency||Clozapine (Clozaril®)|
|Thioridazine (Mellaril®)||Lurasidone (Latuda®)|
|Chlorpromazine (Thorazine®)||Paliperidone (Invega®)|
Recognizing and treating side effects is a key component of pharmacotherapy with antipsychotics. Those afflicted with too many side effects will discontinue therapy and likely relapse.
The first-generation antipsychotic drugs, known as typical antipsychotics, generally have more neurological side effects than second-generation antipsychotics. High-potency drugs have more side effects. High-patency first-generation antipsychotics have a high risk of extrapyramidal side effects (EPS) and a medium risk of sedation. Low potency first-generation drugs have a lower risk of EPS side effects and a high risk of sedation and anticholinergic effects (Jibson, 2020). As a class, antipsychotics often lead to weight gain and sexual side effects (breast tenderness, lack of sexual interest, or erectile dysfunction).
Extrapyramidal side effects include Parkinsonism, tardive dyskinesia, dystonia, and akathisia. The most worrisome neurological side effect is neuroleptic malignant syndrome. Other side effects include constipation, blurred vision, sedation, urinary retention, dry mouth, confusion, and orthostatic hypotension.
The atypical antipsychotic drugs have less risk of neurological side effects but are not without risk. These agents may cause weight gain, diabetes, and abnormal cholesterol levels. Antipsychotics may cause weight gain and diabetes, but weight gain and diabetes may be reversed when the drug is stopped.
- Inform patients on home therapy not to alter or discontinue their drug. These drugs should be tapered gradually to discontinue treatment.
- Educate the patient to wear sunscreen when outside, rise slowly from a lying or sitting position and avoid hot tubs.
- Monitor blood pressure.
- Evaluate for extrapyramidal symptoms such as akathisia, dystonia, pseudo-Parkinsonism, and dyskinesia.
- Wear sunscreen or protective clothing to prevent sunburns.
- Take extra precautions during hot weather to avoid heatstroke.
- Drowsiness or impaired mental and motor activity occurs during the first two weeks of taking the drug but tends to decrease over time.
- The sudden appearance of sores in the mouth or a sore throat may indicate agranulocytosis. The patient should contact the prescribing physician if this occurs.
Two drugs are used to manage Alzheimer’s disease - cholinesterase inhibitors and N-methyl-D-aspartate (NMDA) receptor antagonists.
Patients with Alzheimer’s disease have a reduced amount of acetylcholine with resultant reduced cortical cholinergic function. Cholinesterase inhibitors enhance the cholinergic transmission in the synaptic cleft as it inhibits the enzyme cholinesterase.
Donepezil, galantamine, and rivastigmine are three currently available cholinesterase inhibitors. Patients show variable responses to cholinesterase inhibitors, with some patients having profound benefits and others demonstrating minimal to no benefit. Therefore, nurses should assess the efficacy of these drugs on all patients. Patients who do not have a good clinical benefit from one drug may benefit from another drug in the same class.
Common side effects of cholinesterase inhibitors include headaches, dizziness, diarrhea, nausea, anorexia, muscle cramps, and nightmares. Side effects may be minimized by slow titration.
Donepezil (Aricept®) is started at 5 mg every night for four weeks and then titrated up to 10 mg every night. It is well tolerated and available as a pill and an orally disintegrating tablet. It is approved for mild, moderate, and severe dementia.
Donepezil also comes as a 23 mg dose, approved for those with moderate to severe Alzheimer’s disease who have been on donepezil 10 mg for at least three months. In those with moderate to severe dementia, the 23 mg dose was associated with improved cognition but no difference in overall functioning and more side effects (Farlow et al., 2010).
Common side effects of donepezil include nausea, vomiting, and diarrhea. Bradycardia can arise and may slow the heart rate to a point associated with syncope.
Rivastigmine (Exelon®) is approved for mild to moderate dementia and Parkinson’s disease dementia. Common side effects include headache, nausea, vomiting, anorexia, and weight loss. Rivastigmine should be taken with food to reduce gastrointestinal (GI) side effects.
Rivastigmine also comes in a patch form associated with less nausea and vomiting. The patch is available in two doses: 4.6 mg/24 hours and 9.5 mg/24 hours. The lower dose patch has fewer side effects than the oral or high dose patch (Birks et al., 2015).
Galantamine (Razadyne®) is used in mild to moderate Alzheimer’s dementia. It is dosed twice a day in the standard form and once a day in the extended-release form. Side effects include anorexia, weight loss, nausea, vomiting, and diarrhea.
Memantine (Namenda®) is the only N-methyl-D-aspartate (NMDA) receptor antagonist and is approved for moderate-to-severe dementia. Side effects include dizziness, confusion, headache, cough, and constipation, but they are not common. Like cholinesterase inhibitors, the side effects are minimized when the dose is titrated.
Memantine may aid in the treatment of dementia partly through its ability to help control behavior issues, as it has been shown to manage agitation and aggression (Ford & Almeida, 2017). Combining memantine and a cholinesterase inhibitor may have extra benefits when combined.