NURS 6521 Week 8 Discussion: Comparing and Contrasting Pharmacologic Options for the Treatment of Generalized Anxiety Disorder Essay

NURS 6521 Week 8 Discussion: Comparing and Contrasting Pharmacologic Options for the Treatment of Generalized Anxiety Disorder Essay

According to DSM-5, Generalized Anxiety Disorder ( GAD) is characterized by excessive anxiety and worry about events or activities, and the individual finds this hard to control. This condition begins gradually, usually in childhood or adolescence, and may continue to adulthood if not properly managed, with symptoms worsening during periods of stress. Females are twice more likely to suffer from GAD than males. Growing evidence shows that this condition is caused by maladaptive responses in parts of the brain to stressful situations. It is also associated with the impaired function of CNS modulators such as serotonin (5-HT) and gamma-aminobutyric acid (GABA). Various drug and non-drug therapies for managing GAD exist, and these can be used singly or together to ensure holistic patient care.

Treatment Options for Generalized Anxiety Disorder

As you have stated, pharmacotherapy and psychotherapy are essential for managing GAD. The first line psychotherapy for GAD management is Cognitive Behavioral Treatment (CBT). For effective CBT, a triad of interventions consisting of psychoeducation, exercise, and psychosocial support needs to be incorporated (Apolinário-Hagen, 2020). Psychoeducation involves educating the patient on the psychophysiology of the disease and the rationale of the therapeutic interventions being provided. The patient is also encouraged to practice mindfulness, problem-solving, critical thinking, and breathing exercises. Exercise prescription includes jogging and walking training. These can be used as an adjunct to pharmacotherapy.

Selecting a suitable treatment for GAD patients depends on age, comorbidities, and prior treatment. The first line of treatment is usually Selective Serotonin Reuptake Inhibitors ( SSRIs) and Selective Norepinephrine Reuptake Inhibitors (SNRIs). Buspirone, benzodiazepines, and pregabalin can be used as add-on treatments or can be used singly. SSRIs function by increasing synaptic 5-HT concentration. This is attained by inhibition of the 5-HT presynaptic transporter. The downstream effect of increased serotonin neurotransmission has been found useful for alleviating anxiety and improving moods (Melaragno, 2021). SNRIs inhibit the norepinephrine reuptake transporter, increasing norepinephrine synaptic concentration and neurotransmission. Escitalopram and paroxetine are FDA-approved SSRIs, other SSRIs may also be off-label.

Sertraline (Zoloft) is an antidepressant that functions as an SSRI. It is slowly absorbed following oral administration and undergoes significant first-pass metabolism; food increases absorption. It has an elimination half-life of 22 – 36 hours and is metabolized into ketones and alcohol, which are excreted renally as conjugates. It minimally inhibits the CYP-450 enzyme, thus increasing the plasma concentration of drugs metabolized by this enzyme. Sertraline is tolerable more than other SSRIs; however, its primary adverse effects include nausea, dizziness, confusion, somnolence, diarrhea, tremors, and sexual dysfunctions. It has also been associated with dose-dependent QT prolongation and thus should be monitored closely in patients with cardiovascular comorbidities (Garakani,2020). In geriatric patients, its use may cause a Syndrome of Inappropriate Antidiuretic Hormone (SIADH) and thus should be monitored. It is also contraindicated in pregnant mothers, especially during the first trimester; its use has been associated with neonatal cardiovascular defects. Interactions with other serotonin modulators may be life-threatening as this would cause serotonin syndrome; thus, patient education is necessary. Concomitant use of alcohol and sertraline may potentiate the side effects of the drug. This drug is generally safe for use within therapeutic doses.

Pregabalin is an add-on medication that can be administered concomitantly with SSRIs and SNRIs. Pregabalin is an anticonvulsant  gabapentinoid derived from GABA. It binds the alpha -2-delta subunit of voltage-gated calcium channels and functions to reduce their excitability, thus causing CNS inhibition. A significant barrier to the use of pregabalin has been the cost, but with the introduction of multiple generic variants, the drug is more accessible (Chincholkar, 2020). Side effects include weight gain, dizziness, and visual disturbances. It is contraindicated in patients with renal impairments, and dose adjustments must be made. Due to its multiple clinical uses, it is often used for patients with anxiety disorders and other comorbidities.

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Benzodiazepines are a useful drug class for GAD management. They function by binding GABA receptors and increasing the frequency of chloride channel opening. The influx of negatively charged chloride ions into the neurons reduces CNS excitability. These drugs include diazepam (Valium) and lorazepam (Ativan). They are highly protein bound but efficiently distribute across the blood-brain barrier due to their lipophilicity. They undergo extensive hepatic metabolism, some via the glucuronidation process and others via CYP 450 pathway, thus having varying drug-drug interactions (Rosenbaum, 2020). Side effects include drowsiness, poor coordination, and psychomotor slowing.

Benzodiazepines are recommended for short-term use due to increased risks of addiction and dependence (Lewis, 2019). In geriatrics, they may result in cognitive impairment and thus are contraindicated.

Your discussion is detailed and exact and gives an in-depth explanation of the management of GAD. This information helps decrease morbidity and mortality that may result from this disorder and provide holistic patient care by ensuring the patient’s physical, psychological, and emotional well-being. 

References

Apolinário-Hagen, J., Drüge, M., & Fritsche, L. (2020). Cognitive behavioral therapy, mindfulness-based cognitive therapy and acceptance commitment therapy for anxiety disorders: Integrating traditional with digital treatment approaches. Advances in Experimental Medicine and Biology, 291–329. https://doi.org/10.1007/978-981-32-9705-0_17

Chincholkar, M. (2020). Gabapentinoids: Pharmacokinetics, pharmacodynamics and considerations for clinical practice. British Journal of Pain, 14(2), 104–114. https://doi.org/10.1177/2049463720912496

Garakani, A., Murrough, J. W., Freire, R. C., Thom, R. P., Larkin, K., Buono, F. D., & Iosifescu, D. V. (2020). Pharmacotherapy of anxiety disorders: Current and emerging treatment options. Frontiers in Psychiatry, 11. https://doi.org/10.3389/fpsyt.2020.595584

Lewis, G., Duffy, L., Ades, A., Amos, R., Araya, R., Brabyn, S., Button, K. S., Churchill, R., Derrick, C., Dowrick, C., Gilbody, S., Fawsitt, C., Hollingworth, W., Jones, V., Kendrick, T., Kessler, D., Kounali, D., Khan, N., Lanham, P., … Lewis, G. (2019). The clinical effectiveness of sertraline in primary care and the role of depression severity and duration (panda): A Pragmatic, double-blind, placebo-controlled randomised trial. The Lancet Psychiatry, 6(11), 903–914. https://doi.org/10.1016/s2215-0366(19)30366-9

Melaragno, A. J. (2021). Pharmacotherapy for anxiety disorders: From First-line options to treatment resistance. FOCUS, 19(2), 145–160. https://doi.org/10.1176/appi.focus.20200048

Rosenbaum, J. F. (2020). Benzodiazepines: A perspective. American Journal of Psychiatry, 177(6), 488–490. https://doi.org/10.1176/appi.ajp.2020.20040376 , J. F. (2020).

Please reply to Kerisha Gooden-Gordon on her discussion regarding prescribing a single kind of medication or multi medications for the management of generalized anxiety disorder.

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Week 8 Discussion: Comparing and Contrasting Pharmacologic Options for The Treatment

Of Generalized Anxiety Disorder

Initial Post

Generalized Anxiety Disorder

Generalized anxiety disorder (GAD) is a chronic condition characterized by uncontrollable worrying with unrealistic or excessive anxiety about several events or activities such as work or school performance that lasts 6 months or longer (McCance & Huether, 2019; Rosenthal & Burchum, 2021). Studies have reported that GAD is relatively common, with an estimated lifetime prevalence of 4.3% in the general population, 2% to 6% of adults, and twice as many women as men have GAD, and 6.1 million Americans are affected (Arcangelo, et al. 2021; Carl, et al. 2020). Genetics has played a part in GAD; family history is noted frequently in this disorder. According to Baldwin (2022), genetic factors appear to predispose individuals to the development of GAD which shares a common heritability with major depression and with the personality trait of “neuroticism”. Additionally, variations in subtypes of glutamic acid decarboxylase gene as increasing susceptibility to GAD and increased frequency of the serotonin transporter gene-linked polymorphic region SS genotype are noted in these individuals (Baldwin, 2022).

Treatment options for Generalized Anxiety Disorder.

Generalized anxiety disorder (GAD) can be managed with drugs and non-drug therapy drugs. Nondrug approaches include supportive therapy, cognitive behavioral therapy (CBT), biofeedback, and relaxation training, and are usually helpful when symptoms are mild. Nondrug therapy approaches aim to help relieve symptoms and improve coping skills in anxiety-provoking situations (Rosenthal & Burchum, 2021). Drugs may be indicated in instances when symptoms are intensely uncomfortable or disabling, current U.S. Food and Drug Administration (FDA)–approved first-line and second-line choices (Rosenthal & Burchum, 2021). First-line choices include SRIs (including both SSRIs and SNRIs) and buspirone. Second-line choices include benzodiazepines. With benzodiazepines, the onset of relief is rapid. In contrast, with buspirone and antidepressants, onset is delayed. Accordingly, benzodiazepines can be utilized for immediate stabilization, especially when anxiety is severe. However, for long-term management, buspirone and antidepressants are preferred (Rosenthal & Burchum, 2021).

Pharmacokinetics and Pharmacodynamics of medications used to treat GAD.

Selective serotonin reuptake inhibitors (SSRIs) and serotonin-norepinephrine reuptake inhibitors (SNRIs) are antidepressants that also work to treat anxiety symptoms and have the most evidence to support their use and have a lower risk of side effects compared to other medication options. SSRIs and SNRIs can take about a month to start reducing anxiety symptoms. The U.S. Food and Drug Administration (FDA) approved SSRIs to treat GAD are Escitalopram (Lexapro) and paroxetine (Paxil). All SSRIs work similarly do have some common side effects including increased anxiety when first starting the SSRI, diarrhea, headaches, nausea, dry mouth, and sexual side effects, like erectile dysfunction (ED) or lowered sex drive, (Drugs.com, 2023). Escitalopram (Lexapro) is well absorbed following oral administration, with peak plasma concentration usually attained within 5 hours. Food does not affect absorption and is extensively metabolized in the liver to less pharmacologically active metabolites by multiple enzyme systems, including CYP3A4 and CYP2C19, and is eliminated principally in urine with a half-life of 27 – 32 hours, (Drugs.com, 2023). SNRIs include medications like venlafaxine (Effexor XR) and duloxetine (Cymbalta) which are FDA-approved to treat GAD. SNRIs can cause side effects, including Nausea, Dry mouth, Tiredness, Constipation, and Sweating. While both these SNRIs can cause sexual problems, like erectile dysfunction, it’s more likely with venlafaxine. Duloxetine is more likely to cause a headache (Drugs. Com 2022). Venlafaxine is well absorbed.

Buspirone is an anti-anxiety medication that’s FDA-approved to treat GAD. It’s often added to an SSRI or SNRI if anxiety symptoms are not fully controlled. Although it is well tolerated by most people it sometimes causes mild side effects, like dizziness, drowsiness, nervousness, sedation, lightheadedness, excitement, and nausea. Levels of buspirone can be greatly increased by grapefruit juice, erythromycin, and ketoconazole. Buspirone does not enhance the depressant effects of alcohol, barbiturates, and other general CNS depressants. No withdrawal symptoms have been observed on termination and appear to have no potential for abuse choices (Rosenthal & Burchum, 2021).

Benzodiazepines are FDA-approved to treat GAD symptoms, first-choice drugs for the treatment of acute anxiety, and work well to treat anxiety over short periods. Benzodiazepines such as diazepam (Valium), alprazolam (Xanax), and lorazepam (Ativan) are commonly used. Benefits derive from enhancing responses to GABA, an inhibitory neurotransmitter that is immediate, and the margin of safety is high. Side effects are sedation and psychomotor slowing. Because of their abuse potential, benzodiazepines should be used with caution in patients known to abuse alcohol or other psychoactive substances. Long-term use of benzodiazepines carries a risk of physical dependence. Withdrawal symptoms include panic, paranoia, and delirium. To minimize withdrawal symptoms, benzodiazepines should be tapered gradually—over several months (Rosenthal & Burchum, 2021).

Conclusion

Advanced practice nurses have a responsibility to ensure the safe and effective diagnosis, treatment, and education of patients with psychological disorders. In doing so, the goal of therapy to reduce the patient’s anxiety, and depressive symptoms, return the patient to a normal level of functioning with minimal side effects, and improve the patient’s quality of life is paramount (Arcangelo, et al. 2021). Nonpharmacologic therapy such as cognitive therapy treats anxiety as faulty thought pattern that evokes symptoms of anxiety, fear of dying, loss of control. Cognitive therapy combined with pharmacological therapy is said to produce greater therapeutic response (Arcangelo, et al. 2021).

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References

Arcangelo, V. P., Peterson, A. M., Wilbur, V., & Kang, T. M. (2021). Pharmacotherapeutics for

advanced practice: A Practical Approach (5th ed.) Wolters Kluwer Health.

Baldwin, D. (2022). Generalized anxiety disorder in adults: Epidemiology, pathogenesis, clinical

manifestations, course, assessment, and diagnosis. https://www.uptodate.com/contents/generalized-anxiety-disorder-in-adults-epidemiology-pathogenesis-clinical-manifestations-course-assessment-and-diagnosis?search=generalized%20anxiety%20disorder%20treatment&source=search_result&selectedTitle=5~150&usage_type=default&display_rank=5

Carl, E., Witcraft, S. M., Kauffman, B. Y., Gillespie, E. M., Becker, E. S., Cuijpers, P., Van

Ameringen, M., Smits, J. A. J., & Powers, M. B. (2020). Psychological and pharmacological treatments for generalized anxiety disorder (GAD): a meta-analysis of randomized controlled trials. Cognitive Behaviour Therapy, 49(1), 1–21. https://doi.org/10.1080/16506073.2018.1560358

Drugs.com (2022). Effexor XR Prescribing Information.

https://www.drugs.com/pro/effexor-Links to an external site.xr.html

Drugs.com (2023). Escitalopram (Monograph).

https://www.drugs.com/monograph/escitalopram.html

McCance, K. L., & Huether, S. E. (2019). Pathophysiology: The biologic basis for disease in adults and children (8th ed.). St. Louis, MO: Mosby/Elsevier.

Rosenthal, L. D., & Burchum, J. R. (2021). Lehne’s pharmacotherapeutics for advanced practice

nurses and physician assistants (2nd ed.) St. Louis, MO: Elsevier.