NURS 6521 COMPARING AND CONTRASTING PHARMACOLOGIC OPTIONS FOR THE TREATMENT OF GENERALIZED ANXIETY DISORDER

Generalized anxiety disorder (GAD), a chronic condition, frequently starts in adolescence or the early stages of adulthood and lasts the rest of one’s life (Strawn et al., 2018). The medications include selective serotonin reuptake inhibitors (SSRIs) and serotonin-norepinephrine reuptake inhibitors (SNRIs). These are Antianxiolytics, which typically affect the brain’s neurotransmitters inhabiting reuptakes in terms of their pharmacokinetics and pharmacodynamics.

Selective Serotonin Reuptake Inhibitors (SSRIs) and serotonin-norepinephrine reuptake inhibitors (SNRIs) are considered the first line of drugs to treat generalized anxiety disorder. The main mechanism of action of SSRIs is to prevent presynaptic serotonin reuptake at the serotonin transporter, which raises serotonin levels at the postsynaptic membrane in the serotonergic synapse (Edinoff et al., 2021). These medications include fluoxetine, Citalopram, escitalopram, paroxetine, sertraline, and fluvoxamine. These medications treat generalized anxiety disorder using the same mechanism. However, each of them has unique pharmacokinetics and pharmacodynamics. The half-life of each drug varies, for instance, fluoxetine’s half-life is 1 to 4 days, whereas Citalopram’s half-life is 26 hours. SSRIs tend to be metabolized by cytochrome P450 in the liver. SSRIs tend to have better specificity than MAOIs and TCAs, which makes them the drug of choice for treating depression as well. The side effects of these medications include weight gain, sleepiness, and dry mouth.

Different Treatment Options:

Antihistamines, such as Hydroxyzine are one of the most common FDA-approved medications that could be used for anxiety as well. Antihistamines, such as hydroxyzine, are histamine-1 receptor (H1) blockers that are frequently used as an alternative to benzodiazepines for anxiety, panic attacks, and sleeplessness (Garakani et al., 2020). Though antihistamines are used for allergy symptoms, Hydroxyzine and Diphenhydramine (Benadryl) may be safer for adolescents and in pregnancy for anxiety symptoms as well. Aside from side effects including dry mouth, constipation, and sedation, antihistamines are generally well tolerated.

NURS 6521 COMPARING AND CONTRASTING PHARMACOLOGIC OPTIONS FOR THE TREATMENT OF GENERALIZED ANXIETY DISORDER

Cannabis may have potential therapeutic effects in treating anxiety. Cannabis is known for its pleasurable and calming effects. Additionally, preclinical studies show that CBD has antidepressant effects after both acute and long-term dosing (Martin et al., 2021). The use of cannabis and other cannabinoids is accepted as a safe means of promoting relaxation and reducing anxiety, however there is not much literature or evidence that supports that.

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Benzodiazepines are one the treatment for anxiety and remain one of the most commonly used classes of psychiatric drugs worldwide. Benzodiazepines, which function as GABA-A agonists, are very adaptable drugs that can be administered for a variety of disorders. They can be used for mania, insomnia, anxiety, agitation, and seizures. However, antidepressant effectiveness may be decreased by long-term usage of benzodiazepines to treat anxiety and co-morbid depression (Garakani et al., 2020).

Edinoff, A. N., Akuly, H. A., Hanna, T. A., Ochoa, C. O., Patti, S. J., Ghaffar, Y. A., Kaye, A. D., Viswanath, O., Urits, I., Boyer, A. G., Cornett, E. M., & Kaye, A. M. (2021, August 5). Selective serotonin reuptake inhibitors and adverse effects: A narrative review. Neurology international. Retrieved January 14, 2023, from https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8395812/

Garakani, A., Murrough, J. W., Freire, R. C., Thom, R. P., Larkin, K., Buono, F. D., & Iosifescu, D. V. (2020, December 23). Pharmacotherapy of anxiety disorders: Current and emerging treatment options. Frontiers in psychiatry. Retrieved January 15, 2023, from https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7786299/#:~:text=in%20anxiety%20disorders.-,Antihistamines,approved%20for%20use%20in%20anxiety.

Martin, E. L., Strickland, J. C., Schlienz, N. J., Munson, J., Jackson, H., Bonn-Miller, M. O., & Vandrey, R. (2021, September 9). Antidepressant and anxiolytic effects of medicinal cannabis use in an observational trial. Frontiers in psychiatry. Retrieved January 15, 2023, from https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8458732/

Strawn, J. R., Geracioti, L., Rajdev, N., Clemenza, K., & Levine, A. (2018, July). Pharmacotherapy for generalized anxiety disorder in adult and pediatric patients: An evidence-based treatment review. Expert opinion on pharmacotherapy. Retrieved January 14, 2023, from https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6340395

While cannabis can be a non-pharmacological route to help deal with anxiety, it can also cause it. The biphasic effect of cannabinoids on anxiety can be viewed as a consequence of cannabinoid regulation of GABA/glutamate balance. Acting on GABAergic terminals may increase anxiety and acting on glutamatergic terminals may decrease anxiety. “The plant’s anxiety-modulating action has largely been attributed to a biphasic interaction with the CB1 receptor. Rey et al. (2012) found that the anxiolytic effects of low doses occur when they interact with the CB1 receptor on cortical glutamatergic terminals. Conversely, interaction with the CB1 receptor on the GABAergic terminals is responsible for anxiogenesis, something which takes place when higher doses are administered.”

Components of CBT include teaching patients to identify and label irrational thoughts and to replace them with positive self-statements. The cognitive modification approaches are combined with behavioral treatments such as exposure or relaxation training. In the article. it states that CBT significantly reduces anxiety symptoms post treatment in patients with generalized anxiety disorder.Compared with usual care, treatment with structured psychotherapy (CBT or interpersonal therapy) represents good value for money for adults with major depressive disorder and/or generalized anxiety disorder.”

References

(2018, November 13). Psychotherapy for major depressive disorder and generalized anxiety disorder: A Health Technology Assessment. Ontario health technology assessment series. Retrieved January 17, 2023, from https://pubmed.ncbi.nlm.nih.gov/29213344/

Sharpe, L., Sinclair, J., Kramer, A., de Manincor, M., & Sarris, J. (2020, October 2). Cannabis, a cause for anxiety? A critical appraisal of the anxiogenic and anxiolytic properties. Journal of translational medicine. Retrieved January 17, 2023, from https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7531079/

Thank you for the information regarding treatment for GAD during pregnancy. It is important to recognize treatment options that are safe to take during this time because GAD can be common perinatal and postpartum. Not treating GAD during pregnancy can have a negative impact on infants due to decrease responsiveness from mothers and increased stress (Misri et al., 2015). It has been researched that SSRIs and SNRIs cross the placenta and can cause birth defects. Third-trimester exposure to SSRIs can cause withdrawal symptoms like jitteriness, irritability, tremors, difficulty feeding, sleeping, hypertonia, and seizures. Benzodiazepines can also cause cleft lips, withdrawal symptoms, and floppy infant syndrome.

Medications that are safe to take during pregnancy include sertraline, fluoxetine, mirtazapine, fluvoxamine, and paroxetine. Still, they should be discussed with the patient as they can cause various symptoms (Ballone et al., 2020). For example, fluoxetine and sertraline can promote inefficient weight gain during pregnancy and should be closely monitored. Fluvoxamine can also cause nausea and vomiting and should not be used in those who are experiencing these symptoms during pregnancy. It is also essential that the expecting mother is referred to the proper resources for mental health services to ensure they are receiving the treatment they need.

References

Ballone, N. T., Moffit, C., Becker, M. A. (2020). Conventional and Integrative Approaches to Treating Anxiety in Pregnancy. Pregnancy Times, 36(8). 40-42. https://cdn.sanity.io/files/0vv8moc6/psychtimes/b7e497b9d63e9cd6dca1ca109f82b2d9a52e7881.pdf/PSY0820_ezine_corrected.pdf Misri S, Abizadeh J, Sanders S, Swift E. Perinatal Generalized Anxiety Disorder: Assessment and Treatment. J Womens Health (Larchmt). 2015 Sep;24(9):762-70. doi: 10.1089/jwh.2014.5150. Epub 2015 Jun 30.

Anxiety disorder is the brain’s typical reactions to activities occurring in an individual’s surroundings. The primary cause of anxiety disorder is genetics and hormone imbalance in the brain’s cellular organs. An example of anxiety disorder occurs when an individual experiences excessive panic and fear of their environment (Cabrera et al., 2020). I agree with you that generalized anxiety disorder causes considerable stress to patients as they have to worry about work and activities of daily living. The condition majorly affects older adults since they are concerned about their health, money, work performance, and even family. The diagnostic process may commence when an individual can no longer control their worrying condition (Canuto et al., 2018). Some of the significant symptoms of a generalized anxiety disorder include feeling nervous, having a sense of impending danger, rapid breathing, feeling weak and tired, and lack of concentration at the workplace and even developing trouble sleeping. The generalized anxiety disorder treatment process involves the therapy and administration of medication to the patient to assist in controlling symptoms such as lack of sleep and even headache. Regards!

References

Cabrera, I., Brugos, D., & Montorio, I. (2020). Attentional biases in older adults with generalized anxiety disorder. Journal of Anxiety Disorders, 45(9), 102207–102211. https://doi.org/10.1016/j.janxdis.2020.102207Links to an external site. Canuto, A., Weber, K., Baertschi, M., Andreas, S., Volkert, J., Dehoust, M. C., … & Crawford, M. J. (2018). Anxiety disorders in old age: psychiatric comorbidities, quality of life, and prevalence according to age, gender, and country. The American Journal of Geriatric Psychiatry, 26(2), 174-185

The way you approached and articulated the discussion is commendable on generalized anxiety disorder (GAD) and the pharmacological approaches to treatment. Indeed, selective serotonin reuptake inhibitors and Serotonin Norepinephrine Reuptake Inhibitors (SNRI) are considered first-line treatments. The medications are effective and well tolerated, with usually manageable or short-lived adverse effects. However, sexual dysfunction is often long-lived, and problematic adverse effects with SNRIs and SSRIs are often manageable with adjunct treatment (Garakani et al., 2020). It is essential to consider that SSRIs and SNRIs were developed as antidepressants, and emerging evidence supported their use in anxiety disorders. They are effective in comorbid depression and anxiety but equally effective as anxiolytics, even in the absence of a depression (Rosenthal and Burchum, 2020).

In alternative treatment, antihistamines, particularly hydroxyzine and diphenhydramine, have been shown to be effective in anxiety disorders, with comparable effectiveness to benzodiazepines. However, it is essential to note that while they offer safer alternatives to benzodiazepines in children and pregnant women, there as significant safety concerns in older adults. Notably, antihistamines pose a high risk of anticholinergic toxicity or delirium in older adults or patients with neurocognitive disorders (Gakarani et al., 2020). According to Stahl (2020), hydroxyzine should be avoided in older adults, especially in dementia. Regarding the use of cannabis, while there is a lack of research on its use in GAD, emerging evidence shows it has no significant clinical benefit. In a study that included 5,075 on cannabis, 90% did not experience significant improvement based on the GAD-7 score over an average of 282 days of follow-up. Only 3.7% had a clinically significant decrease (Lee et al., 2022). Still, there are significant safety concerns about using cannabis for anxiety. According to Stanciu et al. (2021), medical cannabis should not be recommended for treating patients with anxiety disorders, with the concern of worsening anxiety disorders and inducing psychotic symptoms.

References

Garakani, A., Murrough, JW., Freire, RC., Thom, RP., Larkin, K., Buono, FD., & Iosifescu, DV. (2021). Pharmacotherapy of Anxiety Disorders: Current and Emerging Treatment Options. Focus (American Psychiatric Publishing), 19(2), 222–242. https://doi.org/10.1176/appi.focus.19203Links to an external site.

Lee, C., Round, JM., Klarenbach, S., Hanlon, JG., Hyshka, E., Dyck, J. RB., & Eurich, DT. (2021). Gaps in evidence for the use of medically authorized cannabis: Ontario and Alberta, Canada. Harm reduction journal, 18(1), 61. https://doi.org/10.1186/s12954-021-00509-0Links to an external site.

Rosenthal, LD., & Burchum, JR. (2021). Lehne’s Pharmacotherapeutics for Advanced Practice Nurses and Physician Assistants – E-Book. Elsevier Health Sciences. Kindle Edition.

Stanciu, C. N., Brunette, M. F., Teja, N., & Budney, A. J. (2021). Evidence for Use of Cannabinoids in Mood Disorders, Anxiety Disorders, and PTSD: A Systematic Review. Psychiatric services (Washington, D.C.), 72(4), 429–436. https://doi.org/10.1176/appi.ps.202000189Links to an external site.

GAD is a chronic condition characterized by uncontrollable worrying. (Rosenthal 2018, p.243). Most patients with GAD also have another psychiatric disorder, depression. It usually involves a persistent feeling of anxiety or dread that interferes with how you live your life. “It is not the same as occasionally worrying about things or experiencing anxiety due to stressful life events. People living with GAD experience frequent anxiety for months, if not years. GAD develops slowly. It often starts around age 30, although it can occur in childhood. The disorder is more common in women than in men.” (NIH of Mental Health). Good news, it’s treatable. SSRIs and SNRIs are the first line treatment for GAD.

Of the 13 benzodiazepines available, 6 are approved for anxiety. Benzodiazepines are second-line drugs for anxiety called central nervous system depressants. “They raise levels of an amino acid in your brain called gamma-aminobutyric acid (GABA). blocks other activity in your brain, which helps you feel calm and can make you sleepy. Anxiolytic effects develop slowly with first initial responses to show within a week.They are distinguished by their pharmacokinetics and their metabolism to a large extent; condition their use [3]. These are weak acids of variable constant dissociation with a high lipophilicity, which allows rapid passage through the membranes (blood-brain and placental barriers, and passage in breast milk). ” (Bourin, 2018).

Pregabalin can be used for epilepsy and neuropathy pain, as well as GAD. Pregabalin exerts its anxiolytic effects by potently binding to the alpha2-delta subunit of the voltage-gated N-and P/Q-type calcium channels in central nervous system (CNS) tissue. This causes a decrease in presynaptic calcium currents which modulates the release of neurotransmitters, including glutamate, substance P, and calcitonin gene-related peptide from excited neurons. A decrease in scores on the Hamilton Anxiety Rating Scale was noted with pregabalin within a week and was effective on both somatic and psychic symptoms; shown to be effective in patients over 65 years of age.

References

Bourin, M. (2018, February 12). Clinical Pharmacology of anxiolytics. Archives of Depression and Anxiety. Retrieved January 16, 2023, from https://www.peertechzpublications.com/articles/ADA-4-129.phpLinks to an external site.

Rosenthal, L. D., & Burchum, J. R. (2021). Lehne’s pharmacotherapeutics for advanced practice nurses and physician assistants (2nd ed.) St. Louis, MO: Elsevier.

Links to an external site.

U.S. Department of Health and Human Services. (n.d.). Generalized anxiety disorder: When worry gets out of Control. National Institute of Mental Health. Retrieved January 16, 2023, from https://www.nimh.nih.gov/health/publications/generalized-anxiety-disorder-gad

References

Rosenthal, L. D., & Burchum, J. R. (2021). Lehne’s pharmacotherapeutics for advanced practice nurses and physician assistants (2nd ed.) St. Louis, MO: Elsevier.

Links to an external site.

This is an outstanding discussion post. Indeed, benzodiazepines are approved for anxiety. However, they are second-line drugs for anxiety called central nervous system depressants. As such, it is important to consider first-line medications first before resorting to second-line drugs for anxiety. In this case, the first-line drugs that could be considered include selective serotonin reuptake inhibitors (SSRIs) and serotonin-norepinephrine reuptake inhibitors (SNRIs) (Garakani et al., 2020). In situations where SSRIs or SNRIs fail to work, it is important to consider other options such as buspirone and hydroxyzine. Sometimes these drugs may be prescribed alongside SSRIs or SNRIs. Notably, relying solely on benzodiazepines in the treatment of GAD is discouraged. Benzodiazepines should only be utilized as add-on therapy to other drugs such as SSRI or SNRI and used for short-term. It is important to appreciate the pharmacokinetics and Pharmacodynamics processes of these medications (Shalimova et al., 2021). The eventual goal of prescribing medications to patients is to attain a therapeutic outcome and while minimizing adverse effects. As such, understanding the crucial pharmacokinetic and pharmacodynamic mechanisms of the drugs is essential in developing treatment plans and maximizing use in patients.

References

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, 1412. https://doi.org/10.3389/fpsyt.2020.595584

Shalimova, A., Babasieva, V., Chubarev, V. N., Tarasov, V. V., Schiöth, H. B., & Mwinyi, J. (2021). Therapy response prediction in major depressive disorder: current and novel genomic markers influencing pharmacokinetics and pharmacodynamics. Pharmacogenomics, (0). https://doi.org/10.2217/pgs-2020-0157

I investigated alternative treatments for Gad. Cognitive-behavioral therapy (CBT) is a type of psychotherapy that helps the individual to identify and change negative thought patterns, behaviors, and emotions that contribute to GAD. CBT is based on the idea that the way we think and behave affects our feelings and can be modified to reduce anxiety. Studies have found that CBT can be effective in reducing symptoms of GAD in adults Relaxation techniques, such as progressive muscle relaxation and deep breathing, can help to reduce stress and anxiety by calming the body and mind. Mindfulness and meditation can also help to reduce stress and increase relaxation by allowing the individual to become more aware of the present moment Exercise can be beneficial for those with GAD as it releases endorphins, which can help to reduce stress and improve mood. Nutrition can also play an important role in managing GAD. Eating a balanced diet full of fruits, vegetables, whole grains, and lean proteins can help to regulate hormones and improve overall health, which can help to reduce stress and anxiety. Overall, alternative treatments for GAD in adults can be effective in managing symptoms. While medication can be necessary for some people, alternative treatments can often be used in conjunction with medication to help reduce symptoms. It is important to speak to a doctor or mental health professional to determine the best treatment option for everyone. The effectiveness of alternative treatments for GAD in adults depends on the individual and the treatment chosen. Studies have shown that cognitive-behavioral therapy, relaxation techniques, mindfulness and meditation, exercise, and nutrition can all be effective in reducing symptoms of GAD. However, it is important to speak to a doctor or mental health professional to determine the best treatment option for everyone.

Reference:

Anderson, F. H. (2021, February 10). Treatment – Generalised anxi disorder in adults. nhs.uk. https://www.nhs.uk/mental-health/conditions/generalised-anxiety-disorder/treatment/Links to an external site.

In the residential treatment setting in which I work now, we are treating adolescents for multiple mental health disorders, including depression, GAD, and PTSD. Anxiety is the most common psychiatric disorder in adolescents, with approximately 7% of youths in the world experiencing it. Certain types of anxiety are more commonly displayed at certain ages. With the age group of 13-18, social anxiety GAD and panic are more common. Unfortunately, it can be worsened by family issues, traumatic experiences, and other psychiatric disorders (Walter et al., 2020). While generalized anxiety at a low or moderate level can be managed without medication, even preferably, it can become debilitating at a certain level and especially in combination with other diagnoses. Often, clients come in with common signs, including difficulty sleeping, difficulty concentrating in school, apprehension, restlessness and more physical symptoms when anxiety worsens (Rosenthal & Burchum, 2021).

The first options for medication treatment for GAD include SSRIs and buspirone. With this particular age group, SSRIs are the first choice. SSRIs inhibit the reuptake of serotonin in the brain, which increases its availability. Over time, this leads to a downregulation of the inhibitory autoreceptors, heightening serotonergic firing rate. SSRIs are generally well tolerated and improve symptoms (Walter et al., 2020). When combined with cognitive behavioral therapy (CBT), outcomes are optimal (Garcia & O’Neil, 2021). SNRIs are acceptable as well, but side effects can be less easily tolerated and may require more monitoring. SNRIs inhibit the reuptake of both serotonin and norepinephrine. Duloxetine is the only SNRI to have FDA indication for treating anxiety disorders. Of note, there is warning of increased suicidal thoughts through age 24 when starting any of these medications and increasing dose (Walter et al., 2020).

Research shows that factors linked to long term success with medication treatment include male gender, absence of social phobia, successful initial treatment response, higher global functioning, healthy family dynamics, and few negative life events (Garcia & O’Neil). In the residential treatment center, we are able to closely monitor clients and make changes rather quickly if necessary. They are experiencing a lot of change on many levels while in treatment, including psychological, physical and lifestyle, so it’s vital for all parties involved in their care to communicate and adjust as necessary for the best outcomes. For many clients, we have tried various SSRIs, occasionally an SNRI and make dose adjustments often. When medications are started, we get baseline labs and ECGs as needed and monitor progress and side effects. In this setting, we have the luxury of doing this. If these adolescents were outpatient, I would be following up with them weekly to start to monitor effectiveness and make changes as necessary.

References

Garcia, I and O’Neil, J. (2021). Anxiety in Adolescents. The Journal for Nurse Practitioners, 17(1), 49-53. https://doi.org/10.1016/j.nurpra.2020.08.021 Links to an external site..

Rosenthal, L. D., & Burchum, J. R. (2021). Lehne’s pharmacotherapeutics for advanced practice nurses and physician assistants (2nd ed.) St. Louis, MO: Elsevier.

Walter, H. J., Bukstein, O. G., Abright, A. R., Keable, H., Ramtekkar, U., Ripperger-Suhler, J., & Rockhill, C. (2020). Clinical Practice Guideline for the Assessment and Treatment of Children and Adolescents With Anxiety Disorders. Journal of the American Academy of Child and Adolescent Psychiatry, 59(10), 1107–1124. https://doi.org/10.1016/j.jaac.2020.05.005Links to an external site.

NURS 6521 COMPARING AND CONTRASTING PHARMACOLOGIC OPTIONS FOR THE TREATMENT OF GENERALIZED ANXIETY DISORDER