NURS 6521 Comparing And Contrasting Pharmacologic Options For The Treatment Of Generalized Anxiety Disorder

NURS 6521 Comparing And Contrasting Pharmacologic Options For The Treatment Of Generalized Anxiety Disorder

A Sample Answer For the Assignment: NURS 6521 Comparing And Contrasting Pharmacologic Options For The Treatment Of Generalized Anxiety Disorder

Summary of Patient Case Study

A 71-year-old Asian man with a history of GAD, which was caused by diabetes and hypertension, was presented to our inpatient psychiatric clinic. He was mainly brought for stabilization and long-term medication. The information gathered from the family stated that the patient had refused oral food intake for about thirty hours, was isolative in his room, and had increased confusion.

The diagnosis also showed a history of GAD in the patient’s family, especially among aged people. After admitting him to our clinic, the clinical presentation of the patient depicted a transformed level of consciousness. I took three imperative decisions I thought could help him. They include: stabilizing him, performing psychotherapy, and administering relevant medication.

Evaluation of My Decisions

I believe the decisions I provided were supported by evidence-based literature. According to Watts et al. (2020), psychotherapy involves working with therapists to reduce the level of GAD. For example, in our case, I recommended the therapist to use behavioral therapy because it was the most effective psychotherapy for GAD. On the other hand, stabilizing the patient is imperative because it ensures the conditions of the patient are within the healthy range (Savioli et al., 2020).

For example, in our case, I recommended calming the patient to regain his level of consciousness.  Lastly, I recommended the patient’s medication because it could ease symptoms and prevent or halt hypertension and diabetic conditions (Wilhelmsen & Eriksson, 2019). Medication was the heart of everything because the patient’s issues were beyond anxiety disorders.

Objectives of My Decisions

First, I hoped behavioral therapy could help the patient manage various GAD-related symptoms, such as anxiety and stress. I also expected this treatment option could help the patient cope with negative emotions. Second, I hoped the medication decisions I recommended, such as Crestor 20mg daily, Lantus insulin 10 units daily, Metformin 70mg daily, Lithium 300mg daily, and hydrochlorothiazide 25mg daily, could help the patient improve his hypertension and diabetic conditions.

Lastly, I hoped the patient would be stable after recommending a stabilization program in the emergency room. I also expected his pressure to normalize after calming him by providing personal attention.

Differences between Expectations and Results

In psychotherapy, the expected results were attained. For example, the patient coped with adverse emotions and managed his anxiety and stress. He calmed down and started conversing with me. On the other hand, the prescribed medication also responded positively as planned. For example, in this decision, I aimed to improve the patient’s diabetic condition, which came down to manageable levels. Therefore, there was no difference between the anticipated and results. Lastly, the objectives of my decision to stabilize the patient aligned with the outcomes. For example, the patient’s hypertension was very high, but I managed to bring it to normal levels.

Pharmacokinetics and Pharmacodynamics Processes

In the pharmacokinetics process, the medication I recommended, especially oral medication, undergoes three stages. Absorption is the first stage, where the medicine is ingested and passed through the stomach into the intestine linings. The second stage is distribution, where the drugs pass through the liver and intestines into the bloodstream. The third stage is metabolism, where the drug undergoes glucuronidation and oxidation.

The last stage is the excretion of the medicine, mainly through the functioning of the kidney. The pharmacodynamics commences when the drug reaches the target organ or tissue. The drug may involve enzyme inhibition or cause presynaptic or postsynaptic effects on the patient. The final part of pharmacodynamics involves cellular response and signal transduction.

References

Savioli, G., Ceresa, I. F., Manzoni, F., Ricevuti, G., Bressan, M. A., & Oddone, E. (2020). Role of a brief intensive observation area with a dedicated team of doctors in the management of acute heart failure patients: a retrospective observational study. Medicina, 56(5), 251.

Watts, S., Marchand, A., Bouchard, S., Gosselin, P., Langlois, F., Belleville, G., & Dugas, M. J. (2020). Telepsychotherapy for generalized anxiety disorder: Impact on the working alliance. Journal of Psychotherapy Integration, 30(2), 208.

Wilhelmsen, N. C., & Eriksson, T. (2019). Medication adherence interventions and outcomes: an overview of systematic reviews. European Journal of Hospital Pharmacy, 26(4), 187-192.

Anxiety disorders are the most common mental condition among both children and adults with an increased risk of comorbid mood, significantly contributing to the world’s burden of disease. Epidemiological studies reveal that GAD affects approximately 5% of the entire population regardless of latitude, compromising their quality of life (Hurtado et al., 2020).

For this reason, different types of anxiety medications are available for the management of the various types of anxiety disorders outlined in the DSM-V. This discussion illustrates a comparison of the pharmacokinetics and pharmacodynamics relating to the different pharmacological options for the management of GAD.

Current clinical guidelines recommend the use of different classes of drugs for the management of anxiety disorders such as serotonin and noradrenaline reuptake inhibitors (SNRIs), selective serotonin reuptake inhibitors (SSRIs), tricyclic antidepressants (TCAs), monoamine oxidase inhibitors (MAOI), benzodiazepines and some antipsychotic and anticonvulsant in addition to miscellaneous agents, like 5-HT1A partial agonist, buspirone (Bandelow, 2020).

SSRIs (citalopram, paroxetine, sertraline) and SNRIs (levomilnacipran, duloxetine, desvenlafaxine) have been approved by the FDA as first-line for the management of anxiety disorders in adults. These drugs are recommended as the first-line mainly due to the great association of anxiety disorders with depression, in addition to the fact that they lack the potential for abuse and dependence.

TCAs (amitriptyline, dosulepin, clomipramine) and MAOI (phenelzine, isocarboxazid) are considered second-line for the management of anxiety disorder. However, unlike SSRIs and SNRIs, the use of TCAs and MAOIs are somehow limited in clinical practice due to less favorable safety profiles and side effects such as weight gain, and increased toxicity (Schanzer et al., 2019).

The third line includes drugs such as benzodiazepines, which are potent with rapid anxiolytic effects. However, they are considered controversial agents as a result of their inability to manage co-morbid depression and the associated risks of sedation, dependency, and memory problems.

Generally, several factors must be considered such as patient presenting symptoms, age, race, comorbidities, and overall health status among others, when deciding on what medication to prescribe for anxiety disorders. Consequently, evaluating the pharmacodynamics and pharmacokinetics of the available anxiolytics is crucial to promote the use of only safe and effective drugs for desirable treatment outcomes.

References

Bandelow, B. (2020). Current and novel psychopharmacological drugs for anxiety disorders. Anxiety Disorders, 347-365. https://doi.org/10.1007/978-981-32-9705-0_19

Hurtado, M. M., Villena, A., Vega, A., Amor, G., Gómez, C., & Morales‐Asencio, J. M. (2020). ‘I have anxiety, but I have values and preferences’ Experiences of users with generalized anxiety disorder: A qualitative study. International journal of mental health nursing, 29(3), 521-530. https://doi.org/10.1111/inm.12690

Schanzer, B., Rivas-Grajales, A. M., Khan, A., & Mathew, S. J. (2019). Novel investigational therapeutics for generalized anxiety disorder (GAD). Expert opinion on investigational drugs, 28(11), 1003-1012. https://doi.org/10.1080/13543784.2019.1680638

Psychological disorders, such as depression, bipolar, and anxiety disorders can present several complications for patients of all ages. These disorders affect patients physically and emotionally, potentially impacting judgment, school and/or job performance, and relationships with family and friends. Since these disorders have many drastic effects on patients’ lives, it is important for advanced practice nurses to effectively manage patient care. With patient factors and medical history in mind, it is the advanced practice nurse’s responsibility to ensure the safe and effective diagnosis, treatment, and education of patients with psychological disorders.

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Generalized Anxiety Disorder is a psychological condition that affects 6.1 million Americans, or 3.1% of the US Population. Despite several treatment options, only 43.2% of those suffering from GAD receive treatment. This week you will review several different classes of medication used in the treatment of Generalized Anxiety Disorder. You will examine potential impacts of pharmacotherapeutics used in the treatment of GAD. Please focus your assignment on FDA approved indications when referring to different medication classes used in the treatment of GAD.

To Prepare

• Review the Resources for this module and consider the principles of pharmacokinetics and pharmacodynamics.
• Reflect on your experiences, observations, and/or clinical practices from the last 5 years and think about how pharmacokinetic and pharmacodynamic factors altered his or her anticipated response to a drug.
• Consider factors that might have influenced the patient’s pharmacokinetic and pharmacodynamic processes, such as genetics (including pharmacogenetics), gender, ethnicity, age, behavior, and/or possible pathophysiological changes due to disease.
• Think about a personalized plan of care based on these influencing factors and patient history with GAD.

By Day 3 of Week 8

Post a discussion of pharmacokinetics and pharmacodynamics related to anxiolytic medications used to treat GAD. In your discussion, utilizing the discussion highlights, compare and contrast different treatment options that can be used.

Age as well as racial differences is important factors to be considered when planning a treatment regimen that is therapeutic and effective. Racial differences  in the presentation of anxiety may contribute to under recognition and lack of treatment and hence there is always a difference exist with respect to treatment for anxiety disorders, with African-Americans being less likely than Whites to receive appropriate treatment.

Research states that older African American in the U.S despite of their vulnerability to diverse mental health conditions underuse mental health services and more likely seek help from Primary care providers instead of mental health professionals and less likely to prefer medication as a treatment option. They prefer to seek informal mental health care from spiritual leaders, social service organizations, and the family members as they have negative attitude towards seeking mental health treatment.

Also African- Americans have higher rates of substance use disorders, post-traumatic stress disorders, depression, which places them at increased risk for mental health conditions and suicidal ideation. African- Americans are less likely to seek care for anxiety disorders due to the factors such as negative stigma, racial discrimination in mental health care, lack of access to resources and mistrust of the medical establishment. As per research only about one-quarter of African Americans seek mental health care compared to 40 percent of whites.

It is very important to first figure out there treatment preference which is linked to patient s personal belief on the etiology of his or her disorder as it can help the provider to understand individuals belief behind the disorder for example if the patient prefer psychotherapy may believe their depression is related to psychological stress while those who chose medications as a form of treatment may believe that their mental health disorder is from chemical imbalance. Following their preferred method of treatment is important as it is effective in improving mental health service utilization, treatment outcomes with higher adherence rates.

Hence my first preferred way of treating GAD in older African-American is with cognitive-behavioral therapy especially with trained African- American therapists if possible to remove negative stigmas, mistrust, and barriers such as racial differences. Also I believe since the mental health therapist who has experience working with multicultural or one that  share the same cultural beliefs will be better able to understand their concerns and address them effectively.

By Day 6 of Week 8

Read a selection of your colleagues’ responses and respond to at least two of your colleagues on two different days by suggesting additional factors that might have interfered with the pharmacokinetic and pharmacodynamic processes of the patients diagnosed with GAD. In addition, suggest different treatment options you would suggest to treat a patient with the topic of discussion.

Note: For this Discussion, you are required to complete your initial post before you will be able to view and respond to your colleagues’ postings. Begin by clicking on the “Post to Discussion Question” link, and then select “Create Thread” to complete your initial post. Remember, once you click on Submit, you cannot delete or edit your own posts, and you cannot post anonymously. Please check your post carefully before clicking on Submit!

Comparing and Contrasting Pharmacologic Options for the Treatment of Generalized Anxiety Disorder

There are various pharmacotherapy approaches for the treatment of generalized anxiety disorder. (GAD). The main classes of FDA-approved drugs for the treatment of GAD are selective serotonin, selective norepinephrine reuptake inhibitors (SSRIs and SNRIs), azapirones, and benzodiazepines. An example of an SSRI approved for the treatment of GAD is Sertraline. Sertraline acts by increasing serotonin activity while blocking its reuptake (Garakani et al., 2020). Sertraline shows efficacy and well-tolerability in both adults and children. Additionally, the medication is safe and well-tolerated in the older adult population. While it has low chances of advanced events, the occurrences are higher in the pediatric population compared to adults (Strawn et al., 2018).

Benzodiazepines class of drugs bind GABA to induce feelings of calmness. An example is diazepam. Benzodiazepines are effective for treating GAD with a faster response than SSRIs and SNRIs. Moreover, studies show they give better remission than SSRIs and SNRIs. However, they are not well-tolerated with the pediatric and older adult populations posing the risk of harm (Sartori & Singewald, 2019). Additionally, Benzodiazepines are not commonly prescribed because of the high risk of dependence, abuse, toxicity, and tolerance (Strawn et al., 2018). Due to this, the recommended pharmacotherapy using the medication is 3-6 months, yet this period is not enough for GAD treatment. Hence, people at high risk of abuse should not be given this class of medication.

Azapirones is another class of drug for the treatment of GAD. The only FDA-approved drug from this class is buspirone, an anxiolytic and 5-HT1A receptor agonist (Strawn et al., 2018). The medication effectively treats GAD and is well-tolerated by both adults and the pediatric population. Similarly, the drug is well-tolerated in older adults with no requirement for dose adjustments (Sartori & Singewald, 2019). However, like SSRIs and SNRIs, Azapirones are safer but give lower efficacy than benzodiazepines. Finally, SNRIs like SSNIs act by causing changes in the brain that affect the functioning of neurotransmitters. An example approved for GAD is Effexor, which is well-tolerated and effective for treating GAD in adult and pediatric populations. However, it is associated with pain, weight loss, asthenia, and anorexia (Strawn et al., 2018).

References

Garakani, A., Murrough, J., Freire, R., Thom, R., Larkin, K., Buono, F., & Iosifescu, D. (2020). Pharmacotherapy of Anxiety Disorders: Current and Emerging Treatment Options. Front Psychiatry, 11:595584. https://doi.10.3389/fpsyt.2020.595584. PMID: 33424664; PMCID: PM.

Sartori, S. B., & Singewald, N. (2019). Novel pharmacological targets in drug development for the treatment of anxiety and anxiety-related disorders. Pharmacology & Therapeutics, 204, 107402. https://doi.org/10.1016/j.pharmthera.2019.107402.

Strawn, J., Geracioti, L., Rajdev, N., Clemenza, K., & Levine, A. (2018). Pharmacotherapy for generalized anxiety disorder in adult and pediatric patients: an evidence-based treatment review. Expert Opin Pharmacother, 19(10),1057-1070. https://doi.10.1080/14656566.2018.1491966.

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.

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. 

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.

This is an outstanding discussion post. Indeed, psychotherapy therapy is essential in helping the patient manage various GAD-related symptoms, such as anxiety and stress and also help the patient cope with negative emotions (Lamb et al., 2019). Understanding the pharmacokinetics and Pharmacodynamics in the management of GAD in this case is important. When prescribing medications to this patient, the ultimate goal is to achieve a therapeutic outcome and while reducing adverse effects.

A proper understanding of critical pharmacokinetic and pharmacodynamic properties of the medications is critical in formulating treatment plans entailing medications and also optimizing its utility in patients and supporting the medication development initiative (Abuhelwa et al., 2022). It is important to involve interprofessional team to ensure the safety and efficacy of pharmacokinetic and pharmacotherapy. The patient should be educated on correct self-administration and storage of medications. This education can be conducted by the nurse, pharmacist, or physician.

References

Abuhelwa, A. Y., Somogyi, A. A., Loo, C. K., Glue, P., Barratt, D. T., & Foster, D. J. (2022). Population pharmacokinetics and pharmacodynamics of the therapeutic and adverse effects of ketamine in patients with treatment‐refractory depression. Clinical Pharmacology & Therapeutics. https://doi.org/10.1002/cpt.2640

Lamb, T., Pachana, N. A., & Dissanayaka, N. (2019). Update of recent literature on remotely delivered psychotherapy interventions for anxiety and depression. Telemedicine and e-Health, 25(8), 671-677.https://doi.org/10.1089/tmj.2018.0079

BY DAY 3 OF WEEK 8

Post a discussion of pharmacokinetics and pharmacodynamics related to anxiolytic medications used to treat GAD. In your discussion, utilizing the discussion highlights, compare and contrast different treatment options that can be used.

Generalized Anxiety Disorder (GAD) is a debilitating condition characterized by excessive and uncontrollable worry (Clemenza et al., 2018). It is an illness that often begins in childhood or early adulthood and persists throughout life. “GAD affects up to 5% of children and adolescents and between 3–6% of adults” (Clemenza et al., 2018, p. 1058). Anxiolytic medications are commonly prescribed for GAD, but an individualized treatment approach is crucial, considering the numerous factors that can affect pharmacokinetics and pharmacodynamics.

Pharmacogenetics is critical in determining the patient’s response to anxiolytic medications (Jancic et al., 2023). Genetic variations in drug-metabolizing enzymes and drug transporters can influence the rate of drug metabolism and bioavailability. For instance, individuals with specific CYP2D6 genetic variants may metabolize selective serotonin reuptake inhibitors (SSRIs) differently, potentially requiring dose adjustments or alternative medications. Therefore, pharmacogenetic testing is a valuable tool to guide treatment decisions and minimize adverse effects.

Furthermore, gender differences can significantly impact the pharmacokinetics and pharmacodynamics of anxiolytic medications. For example, women generally metabolize drugs more slowly than men due to variations in body composition and hormonal fluctuations (Mattison & Soldin, 2009). This can result in differences in drug efficacy and side effects. It may be necessary to consider lower initial doses of medications, close monitoring for side effects, or preferential use of SSRIs, which may have a more favorable risk-benefit profile for some female patients.

Ethnicity can influence drug response due to variations in genetics and cultural factors. Certain ethnic groups may have different genetic polymorphisms, leading to differences in drug metabolism (Koenig et al., 2021). Additionally, cultural beliefs and practices can impact patient adherence to medications. Moreover, age-related changes in pharmacokinetics and pharmacodynamics are significant considerations for GAD treatment.

Elderly patients may experience altered drug metabolism and an increased risk of adverse effects (Cassidy & Sheikh, 2000). This population may benefit from medications with a more predictable safety profile, such as SSRIs or serotonin-norepinephrine reuptake inhibitors (SNRIs), over benzodiazepines. Lower initial doses may also be appropriate for older patients to minimize side effects and prevent excessive sedation.

Patient behavior and lifestyle choices can have a substantial impact on treatment effectiveness. Substance use, including alcohol and illicit drugs, can interact with anxiolytic medications and alter their effects (Brady et al., 2013). Non-pharmacological interventions, like cognitive-behavioral therapy (CBT) and relaxation techniques, should be integrated into the patient’s care plan to address the behavioral aspects of GAD and enhance the effectiveness of pharmacotherapy.

Coexisting medical conditions can influence the pharmacokinetics and pharmacodynamics of anxiolytic medications. Patients with GAD and comorbid diseases like liver or kidney impairment may require dose adjustments to ensure therapeutic drug levels and prevent toxicity (Menon et al., 2022). Additionally, individuals with GAD often experience comorbid depression, which may necessitate a tailored approach to medication selection, favoring agents effective for both conditions (Clemenza et al., 2018).

A comprehensive, personalized care plan for a patient with Generalized Anxiety Disorder (GAD) should consider various influencing factors to optimize treatment outcomes. Firstly, pharmacogenetic testing should be prioritized to identify genetic variations in drug metabolism, enabling the selection of the most suitable medications and dosages tailored to the patient’s unique genetic profile (Jancic et al., 2023).

Additionally, gender-specific considerations should be considered, with lower initial medication doses and close monitoring of potential side effects for female patients, and the consideration of Selective Serotonin Reuptake Inhibitors (SSRIs) as a first-line treatment option (Mattison & Soldin, 2009). Moreover, ethnicity-specific adaptations are essential, customizing medication choices and dosages based on the patient’s ethnicity and considering genetic and cultural factors (Koenig et al., 2021). For elderly patients, a preference for medications with a predictable safety profile, initiating treatment with lower doses, and careful assessment for side effects is crucial (Cassidy & Sheikh, 2000).

Behavioral interventions should also be integrated into the care plan, combining anxiolytic medications with psychotherapy, such as Cognitive-Behavioral Therapy (CBT), and encouraging the adoption of healthy lifestyle choices to address the behavioral aspects of GAD (Brady et al., 2013). Lastly, disease-related adjustments should be made, considering any comorbid medical conditions to ensure that medication choices and dosages are adapted to the patient’s overall health.

When considering treatment options for Generalized Anxiety Disorder (GAD), providers need to consider various factors, such as genetics and age, and each medication’s positive and negative aspects. Benzodiazepines are effective for rapidly alleviating anxiety symptoms, making them suitable for short-term, acute anxiety episodes or as bridge therapy while awaiting the onset of action of SSRIs (Clemenza et al., 2018).

However, they carry the risk of dependence and withdrawal symptoms. They can cause sedation, dizziness, and impaired cognitive function, discouraging long-term use due to the potential for tolerance and addiction.

Selective Serotonin Reuptake Inhibitors (SSRIs) and Serotonin-Norepinephrine Reuptake Inhibitors (SNRIs) are generally considered first-line treatments for GAD due to their safety and efficacy (Clemenza et al., 2018). They have a lower potential for dependence and addiction than benzodiazepines and are suitable for long-term use.

However, their onset of action is slower, often taking several weeks to show therapeutic effects. They may also cause side effects, such as nausea, sexual dysfunction, or weight changes, and genetic factors, like CYP2D6 variations, can influence their metabolism and response (Jancic et al., 2023 & Mayo Clinic, n.d.).

Buspirone provides a non-habit-forming anxiolytic option for GAD. It is suitable for patients who cannot tolerate or prefer to avoid benzodiazepines or SSRIs and can be used as an add-on therapy to SSRIs or SNRIs for enhanced efficacy (Cassidy & Sheikh, 2000). However, it has a slower onset of action compared to benzodiazepines and may be less effective in severe cases of GAD (Gale & Oakley-Browne, 2000). Additionally, buspirone was found to cause more nausea, dizziness, and drowsiness when compared to a placebo.

Combination therapy can simultaneously address multiple aspects of GAD and enhance treatment response, particularly in treatment-resistant cases (Ansara, 2020). It may reduce the need for higher doses of a single medication. However, it increases the risk of drug-drug interactions and side effects, requiring careful monitoring and potential dose adjustments. This approach may also complicate treatment regimens and reduce patient adherence.

Cognitive-behavioral therapy (CBT) and behavioral interventions address GAD’s behavioral and psychological aspects (Ansara, 2020). They effectively teach patients coping skills and anxiety management techniques and can be used alone or as an adjunct to pharmacological treatment.

However, they do not provide immediate relief from symptoms and may be less effective in individuals with severe GAD without concurrent pharmacotherapy. Patient engagement is crucial, and these approaches may only suit some. Therefore, the treatment choice for GAD should be individualized, considering each patient’s unique characteristics and preferences.

BY DAY 6 OF WEEK 8

Read a selection of your colleagues’ responses and respond to at least two of your colleagues on two different days by suggesting additional factors that might have interfered with the pharmacokinetic and pharmacodynamic processes of the patients diagnosed with GAD. In addition, suggest different treatment options you would suggest to treat a patient with the topic of discussion.

Generalized anxiety disorder (GAD) is a condition of uncontrolled feelings of fear, worry, and nervousness; it is often linked with depression (Speed Pharmacology, 2018). GAD can be treated with medication as well as non-pharmaceutical therapy such as cognitive behavioral therapy (CBT) which assist with coping mechanisms to relieve anxiety (Rosenthal et al., 2021). Medications most often used to treat GAD are known as anxiolytics.

Pharmacokinetics of Anxiolytics

Pharmacokinetics of a medication explains how it travels through the body through absorption, distribution, metabolism, and excretion. Anxiolytics also known as anti-anxiety medications consist of benzodiazepines, Barbiturates, and Non-benzodiazepine drugs. Anxiolytics depress the central nervous system (CNS) by being absorbed crossing the blood brain barrier due to their lipid solubility (Rosenthal et al, 2021).

Anxiolytics are metabolized by the liver and excreted by the kidneys. Benzodiazepines metabolize at a different rate than other anxiolytics due to the breaking down of metabolites which can result in longer half-lives of the medication (Rosenthal et al, 2021). Anxiolytics specifically benzodiazepines cause sedation and muscle relation with the CNS including drowsiness, dizziness, impaired coordination, decreased alertness and concentration. Barbiturates have similar effects but they are more significant consisting of a smaller therapeutic range which can result in severe respiratory depression leading to coma and death.

Pharmacodynamics of Anxiolytics

Pharmacodynamics related to anxiolytics involve with a neurotransmitter called GABA which decreases the excitability of neurons (Speed Pharmacology, 2018). Specifically, benzodiazepines increase the effect of GABA by binding to GABA A receptors at alpha gamma site. The increase effect of GABA A receptors decreases excitatory action potentials within the cells. As a result, there is a decrease in anxiety and an increase in calmness within the CNS.

In addition, Barbiturates have a similar affect as benzodiazepines, however they bind at a different site known as alpha beta in the negative chloride ion channel (Speed Pharmacology, 2018). Barbiturates cause the ion channel to open for a longer period of time which cause an inhibitory effect resulting in calming anxiety. On the other hand, non- benzodiazepine anxiolytics have positive effects on anxiety by binding to the alpha 1 site of GABA A receptors (Speed Pharmacology, 2018).

This sub class of medications inhibits sedation which promotes relaxation and sleep to help with anxiety. Lastly, Buspirone is a non-benzodiazepine anxiolytic that is not addictive and is a serotonin agonist which means it causes a decrease in anxiety symptoms by increasing the action of serotonin in the brain (Wilson et al.,2022).

Compare and Contrast Treatment Options

As an inpatient mental health nurse, I am very familiar with patients dealing anxiety which typically is combined with other psychiatric disorders. There are different treatment options for patients with GAD, however treatment plans must be patient specific to ensure positive outcomes. Benzodiazepines although can be very effective in treating GAD, they are also very addicting so they must be prescribed with extreme caution.

There are benefits to prescribing benzodiazepines but I believe that they should be use in a controlled environment such as an inpatient setting to treat acute symptoms of anxiety or panic, alcohol withdrawal, or agitation related to psychosis or mania. These medications are highly abused and oftentimes can result in the need for withdrawal from benzodiazepines due to the addiction factor. Similarly, barbiturates are medications use for sedation to help patients with anxiety be able to relax and sleep.

As a result of their severe sedation effects, they can cause hallucinations, sleep walking, and respiration depression; therefore, I would not recommend these medications for patients who have difficulty sleeping related to GAD (Strawn et al., 2018). Non-Benzodiazepines are sedative/ hypnotics which are also typically prescribed for sleep because of their sedation effects. These medications are recommended to be used short term if patients are having trouble sleeping during an acute episode of anxiety.

SSRI and SNRI

Selective Norepinephrine Reuptake Inhibitor (SSRIs) and Selective Serotonin Reuptake Inhibitor (SNRIs) are not helpful with decreasing physical symptoms often related to anxiety such as chest pain, stomach ache, head ache, panic, and shortness of breath (Rosenthal et al., 2021).

However, these medications increase the level of serotonin in the CNS which can result decreased symptoms of worry, fear, difficulty concentrating, and uncontrolled thinking. In addition, unlike many anxiolytics’ antidepressants are not addictive and can help with long term control of anxiety symptoms when paired with other therapy.

Treatment Plan of GAD

As a future nurse practitioner with mental health experience, I would recommend prescribing alternative medications to anxiolytics as first line treatment for patients with GAD. After reviewing the patient’s medical history including alcohol or drug use, addictive behaviors, co morbidities, and current medications I would recommend an antidepressant along with alternative therapies such as CBT. Specifically, I would start by prescribing an antidepressant such as a SNRI or a SSRI.

In addition to an antidepressant, I would also consider adding Buspirone (anxiolytic) short term until the patient achieves therapeutic effects of the antidepressants which can take up to 2 weeks after onset of treatment (Strawn et al., 2018). In addition, I would recommend CBT to assist the patient with coping skills to assist with decreasing episodes of anxiety and/or panic. Treatment for GAD is most effective when therapy is used in combination with medication (Strawn et al., 2018).

The only times I would consider prescribing anxiolytics aside from Buspirone is if the patient is having acute uncontrolled symptoms with other medications and does not have a history of addiction and would be prescribed as needed and very limited quantity. It is evident that there are many treatment options for patients with GAD and treatment plans should be patient specific depending on their history and severity of symptoms.

References

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

Speed Pharmacology. (2018). Pharmacology – Benzodiazepines, Barbiturates, Hypnotics (Made        Easy) Links to an external site.[Video]. https://www.youtube.com/watch?v=4ZHudeMho8g&t=24s

Links to an external site.

Strawn, J. R., Geracioti, L., Rajdev, N., Clemenza, K., & Levine, A. (2018). Pharmacotherapy for generalized anxiety disorder in adult and pediatric patients: an evidence-based

treatment review. Expert opinion on pharmacotherapy, 19(10), 1057–1070. https://doi.org/10.1080/14656566.2018.1491966

Links to an external site.

Wilson TK, Tripp J. (2022). Stat Pearls: Buspirone. NCBI. https://www.ncbi.nlm.nih.gov/books/NBK531477/

Note: For this Discussion, you are required to complete your initial post before you will be able to view and respond to your colleagues’ postings. Begin by clicking on the Reply button to complete your initial post. Remember, once you click on Post Reply, you cannot delete or edit your own posts and you cannot post anonymously. Please check your post carefully before clicking on Post Reply! 

Pharmacokinetics and Pharmacodynamics Anxiolytic Medications for GAD

Anxiety is a type of medical condition whereby the person feels worried, uneasy, nervous, or stressed. According to the American Psychiatric Association, anxiety is defined as an emotion characterized by feelings of tension, worried thoughts, and physical changes like increased blood pressure. The Diagnostic and Statistical Manual of Mental Health Disorders (DSM-V) classifies anxiety disorders into several main types such as generalized anxiety disorder, panic anxiety, and selective mutism.

Generalized anxiety disorder (GAD) is a type of anxiety that makes a person feel constantly worried. These worrying feelings are about anything and they can last for more than six months. Other symptoms of GAD include nausea, fatigue, trembling, urinating often, sweating hot flashes, irritability, and trouble breathing (Andrews et al., 2010). People diagnosed with GAD are subjected to psychotherapy and medical treatment. The medications used to treat GAD are classified as anxiolytic medications which are a group of drugs used to prevent or treat anxiety symptoms or disorders.

They are sometimes called anti-anxiety medications or minor tranquilizers. Anxiolytic medications are habit-forming and can lead to dependency or a substance use disorder. For this reason, they’re often only prescribed for a short amount of time. Some of the anxiolytic medications include SSRIs (sertraline, fluoxetine, paroxetine, and citalopram). Selective serotonin-norepinephrine reuptake inhibitors (SNRI) such as Venlafaxine and Duloxetine have been approved by FDA as a treatment for GAD. Benzodiazepines (alprazolam) and other types of anxiolytic medications such as Second-generation antipsychotics (SGAs).

 Before prescribing these drugs to any patient, it is important to understand their pharmacokinetics and pharmacodynamics. For example, the pharmacokinetics and pharmacodynamics of benzodiazepines involve the increase of g-aminobutyric acid (GABA) inhibitory impulses in the central nervous system mediated via benzodiazepine receptors. GABA blocks other activity in your brain, which helps you feel calm and can make you sleepy. 

 The structure of benzodiazepines is made up of a benzene ring fused to a seven-membered 1,4 diazepine ring. Alprazolam is administered orally and is directly metabolized by hepatic microsomal oxidation (Jahn et al., 2016). They have a peak plasma concentration which occurs after 1 to 2 hours of being taken. Another drug is chlordiazepoxide which although itself has an intermediate half-life (6 — 28 h), its active metabolite desmethyldiazepam has a very long half-life; oral chlordiazepoxide is rapidly and completely absorbed and its volume of distribution varies from 0.25 to 0.50 l/kg. The drug seems to block electroencephalogram arousal from stimulation in the brain stem reticular formation.

Another type of anxiolytic drug that has been approved to treat GAD is the Selective serotonin reuptake inhibitor (SSRI) drug that works by inhibiting serotonin reuptake transporter and this inhibition of the 5-HT increases the concentration of synaptic hence increasing the extra-synaptic diffusion. An example of SSRIs is fluoxetine which is metabolized through the CYP2D6 system, inhibits CYP2D6 activity, and exhibits considerable intra-individual variability in tolerability and response (Strawn et al., 2018).

It also has noradrenergic and dopaminergic effects which putatively underlie its therapeutic efficacy. SNRI is another type of anxiolytic drug used for treating GAD. An example of SNRI such as venlafaxine has been approved by Food Drug Administration to treat GAD. The pharmacokinetics and pharmacodynamics of venlafaxine work through active metabolite, o-desmethylvenlafaxine by inhibiting the serotonin and norepinephrine reuptake transporters albeit with greater potency at the norepinephrine transporter (Gravelle, 2016).

Duloxetine has been approved by the FDA to treat GAD. Its pharmacodynamics and pharmacokinetics include the reuptake inhibition of serotonin and norepinephrine at the presynaptic neuron in Onuf’s nucleus of the sacral spinal cord ( ).

Another group of anxiolytic medications used is Non-benzodiazepine Sedative-Hypnotics such as eszopiclone which works by interaction with GABA receptor complexes at binding domains located close to or allosterically coupled to benzodiazepine receptors. Other types of anxiolytic medications are Second-generation antipsychotics (SGAs), Antihistamines, GABA-related interventions, and Tricyclic Antidepressants.

  In conclusion, the choice of anxiolytic drug to be prescribed is dependent on the pharmacokinetics and pharmacodynamics factors that might affect the efficacy of the drug. It has been observed that SSRIs and SNRIs are considered the most effective while benzodiazepine and other types of drugs come second.

An expert opinion argues that there is a need for healthcare providers to take an optimal pharmacological approach towards integrative pharmacokinetic and pharmacodynamics optimization strategy that would ensure better treatment and personalization of anxiety disorders. According to Almatura et al. (2013), this approach would help in the development of new anxiolytic drugs that are more effective and have limited side, especially benzodiazepines drugs.

 References

Altamura, A. C., Moliterno, D., Paletta, S., Maffini, M., Mauri, M. C., &Bareggi, S. (2013). Understanding the pharmacokinetics of anxiolytic drugs. Expert opinion on drug metabolism & toxicology, 9(4), 423-440.

Gravielle, M. C. (2016). Activation-induced regulation of GABAA receptors: is there a link with the molecular basis of benzodiazepine tolerance?. Pharmacological Research, 109, 92-100.

Strawn, J. R., Geracioti, L., Rajdev, N., Clemenza, K., & Levine, A. (2018). Pharmacotherapy for generalized anxiety disorder in adult and pediatric patients: an evidence-based treatment review. Expert opinion on pharmacotherapy, 19(10), 1057-1070.

Andrews, G., Hobbs, M. J., Borkovec, T. D., Beesdo, K., Craske, M. G., Heimberg, R. G., … & Stanley, M. A. (2010). Generalized worry disorder: a review of DSM‐IV generalized anxiety disorder and options for DSM‐V. Depression and anxiety, 27(2), 134-147.

Jann, Michael W.; Penzak, Scott R.; Cohen, Lawrence J. (2016). Applied Clinical Pharmacokinetics and Pharmacodynamics of Psychopharmacological Agents || Clinical Pharmacokinetics and Pharmacodynamics of Anxiolytics and Sedative/Hypnotics. , 10.1007/978-3-319-27883-4(Chapter 10), 247–266. doi:10.1007/978-3-319-27883-4_10

D is 46 years white man with history of   generalized anxiety disorder (GAD), hypertension which is being manage with low sodium diet and overweight. To ease his stress at work, he has been self-medicating with alcohol, drinking 3-4 beers per night. Hamilton Anxiety Rate scale (HAM-A) was administered, and JD scored 26. Benzodiazepines, serotonergic reuptake inhibitors (SRIs), and nonbenzodiazepine-nonbarbiturates are some of the pharmacotherapeutic alternatives that might be considered for the treatment of JD’s generalized anxiety disorder (GAD).

Generalized anxiety disorder, also known as GAD, is a chronic illness that can start in early adulthood or even in adolescence and continues throughout an individual’s whole life. The symptoms of GAD can range from mild to severe, but they are almost always debilitating. Behaviors such as excessive concern about ordinary events, somatic complaints, and bodily manifestations are frequently observed. In the United States, a significant percentage of the population struggles with generalized anxiety disorder (GAD).

According to the World Health Organization (2017), anxiety disorders impact around 265 million individuals all over the world. Anxiolytics and other potential medications for the treatment of anxiety disorders are the subject of ongoing study. Anxiolytics are a type of drug for mental health conditions that, in most cases, act on neurotransmitters in the brain. Synaptic activity is improved by the medicine, which also reduces the signs and symptoms of anxiety, leading to an overall improvement in mood.

There are quite a few different approaches to treatment that have been investigated through study. Pharmacological therapies were examined for individuals who had comorbidities (such as major depression and alcohol dependence), as well as the age of the individual. These treatments included the use of selective serotonin and norepinephrine reuptake inhibitors (SSRI and SSNI), as well as benzodiazepines and antiadrenergic medicines.

Kava and lavender oil, both of which belong to the second generation of antipsychotic medication. The research carried out by Strawn (2018) and collaborators identified psychotherapy as an adjunct to pharmaceutical treatment. Both are acting simultaneously, with psychotherapy enhancing adherence and minimizing the consequences of unfavorable outcomes caused by medication.

The process of retaking dopamine and norepinephrine is hindered by a transporter known as selective serotonin re-uptake inhibitors (SSRI). The following are examples of medications that are frequently prescribed: Fluoxetine has a half-life of between four and six days, enhances serotonin transmission, is metabolized in the CYP2D6 yet inhibits activity, and increases serotonin transmission.

Sertraline, the serum level of which reaches its maximum in six to eight hours after administration. Based on a half-life that ranges from 26 to 36 hours and the findings of various studies, it is recommended that the medication be taken twice every day. This is the case after the first four to eight weeks of treatment.

Paroxetine, which inhibits the reuptake of 5-hydroxytryptamine (5-HT) while also blocking the reuptake of norepinephrine, is recommended for the treatment of generalized anxiety disorder (GAD), and this recommendation is backed by the findings of three studies that were conducted with a blinding procedure. and citalopram, which is a protein-bound SSRI that is metabolized by the CYP2C19 enzyme. In comparison to fluoxetine, sertraline, and paroxetine, citalopram is the most selective SSRI.

Benzodiazepines, such as lorazepam (Ativan), are the go-to medication for treating anxiety disorders. In contrast to selective serotonin reuptake inhibitors (SRIs) and nonbenzodiazepine-nonbarbiturates, the therapeutic effects of this medication can be acquired in as little as one dose, making it ideal for the treatment of acute anxiety attacks. There are fewer reported drug interactions with benzodiazepines as well.

The combination of JD’s ongoing alcohol misuse and benzodiazepine use poses a significant risk of profound CNS depression. Prescription of benzodiazepines to those with established substance use disorders also requires consideration of the drug’s addiction potential. Because of this, benzodiazepines are not a good choice for treating JD’s generalized anxiety disorder.

Next, selective serotonin reuptake inhibitors (SRIs) like paroxetine (Paxil) could be tried to treat JD’s generalized anxiety disorder. Since JD is a known substance abuser, the fact that these meds have a limited misuse risk is a bonus. However, serotonin syndrome and other forms of severe toxicity can occur if the medicine accumulates to dangerous levels in the body due to liver damage from heavy alcohol use.

A nonbenzodiazepine-nonbarbiturate like buspirone (Buspar) would be the best prescription option to treat JD’s generalized anxiety disorder (GAD), taking into consideration his medical and social history, as well as his medication profile. It has been claimed that Buspar is just as effective as benzodiazepines, even though it does not depress the central nervous system (CNS) and does not have any potential for misuse (Rosenthal & Burchum, 2021).

In addition, unlike benzodiazepines, it does not amplify the CNS-depressing effects of substances such as alcohol, which makes it an excellent choice for treating JD. In addition to this, it has a low potential for interaction with other medicines.

To make the most of pharmacotherapy in the treatment of JD’s GAD in addition to his other medical conditions, a personalized plan of care needs to be established. This plan of care would take into consideration the entirety of JD’s medical conditions and treatment in addition to his social circumstances to achieve a positive outcome for therapy. First and foremost, JD must be referred to addiction counseling so that methods can be developed to aid him in kicking his drinking habit.

This would be advantageous because, once alcohol consumption is removed from the equation, the prescriber will have a larger range of options to choose from in terms of pharmacotherapy without having to worry about the possibility of adverse drug interactions caused by alcohol consumption. In addition, the inclusion of a component for education is necessary for a personalized care plan to be finished.

JD and whomever take care of him need to receive a substantial amount of education on his pharmacotherapeutic interventions, the action that is supposed to be caused by his prescriptions, the side effects that are to be anticipated, and the ways to treat them. It is imperative that he receives proper education regarding his treatment to maximize the likelihood that he will comply with the prescribed regimen.

In conclusion, the use of medication in the treatment of GAD must be combined with non-pharmaceutical therapies such as cognitive behavior therapy (CBT) and relaxation techniques. These approaches, in addition to the use of medicine, are required to bring about the desired level of anxiety reduction in patients suffering with GAD. Carpenter et al. (2018) proved that cognitive behavioral therapy is only moderately effective in the treatment of anxiety disorders by conducting a meta-analysis of 41 randomized controlled trials in which placebos were also used.

References

Carpenter, J. K., Andrews, L. A., Witcraft, S. M., Powers, M. B., Smits, J. A. J., & Hofmann, S. G. (2018). Cognitive behavioral therapy for anxiety and related disorders: A meta-analysis of randomized placebo-controlled trials. Depression & Anxiety (1091-4269), 35(6), 502–514. https://doi.org/10.1002/da.22728

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.

Strawn, J. R., Geracioti, L., Rajdev, N., Clemenza, K., & Levine, A. (2018). Pharmacotherapy for generalized anxiety disorder in adult and pediatric patients: an evidence-based treatment review. Expert opinion on pharmacotherapy, 19(10), 1057–1070. https://doi.org/10.1080/14656566.2018.1491966

Links to an external site.

World Health Organization. (2017). Depression and Other Common Mental Disorders: Global Health Estimates. Geneva. License: CC BY-NC-SA 3.0 IGO https://www.who.int/publications/i/item/depression-global-health-estimate

Generalized Anxiety Disorder

Week 8 

The name “generalized” anxiety disorder (GAD) comes from the fear of many things rather than just a few. Generalized anxiety disorder (GAD) is a chronic condition characterized by persistent and long-lasting anxiety that typically starts in early adulthood or adolescence and continues throughout an individual’s life (Rosenthal & Burchum, 2021). Visible behaviors include an intense preoccupation with everyday occurrences and the manifestation of somatic and bodily symptoms like tiredness, muscle tightness, and a rapid heartbeat (Rosenthal & Burchum, 2021). 

Pharmacokinetics and pharmacodynamics

Anxiolytics are drugs used for mental health primarily target neurotransmitters in the brain.  The drugs facilitate the activation of synapses to enhance mood and alleviate feelings of anxiety (He, Xiang, Gao, Bai & Fan, 20190). Anxiety can be debilitating, but there are several therapies available to treat GAD.

Non-Drug Therapy

 Therapy that does not include the use of drugs can be used to treat GAD. Supportive therapy, cognitive behavioral therapy (also known as CBT), biofeedback, and relaxation training are examples of alternatives to pharmacological treatment. These things can be helpful in relieving symptoms and improving coping skills in situations that trigger anxiety. When symptoms are relatively minor, treatment using non-drug methods may be sufficient (Rosenthal & Burchum, 2021).

Cannabis

Dragioti, Solmi, Favaro, Fusar-Poli, Dazzan, & Thompson, (2019) posited that there has been an increase in the frequency with which healthcare providers are recommending cannabis to address anxiety problems.   Although there is scarcity of study on the effects of cannabis in comparison to the extensive research conducted on medicine for anxiety.   Conversely, it is shared by Dragioti et al, (2019) that heightened consumption of cannabis can result in heightened levels of anxiety.  

Benzodiazepines

Rosenthal & Burchum, (2021) stressed that benzodiazipine can temporarily be used in the treatment extreme cases of GAD. The chemical structure of benzodiazepines is highly individualized and has consistent pharmacological properties. Due to their pharmacokinetics and metabolism, they should be used cautiously. These weak acids with high lipophilicity and variable constant dissociation cross membranes quickly (blood-brain and placental barriers, breast milk).

Most benzodiazepines are water-insoluble chlordiazepoxide; dipotassium clorazepate, and midazolam, hence organic solutions must be employed for parenteral administration. Short-term anxiety alleviation is usually provided by these sedatives. These medications can be habit-forming, so they should be avoided in patients that misuse alcohol or narcotics.  Benzodiazepines can be administered with SSRIs/SNRIs in the weeks before efficacy (Rosenthal & Burchum, 2021).

Tricyclic antidepressants (TCAs)

 Antidepressants are commonly prescribed to alleviate anxiety symptoms and are frequently administered in conjunction with treatment for depression as well (Rosenthal & Burchum, 2021).  These drugs do not fall within the category of anxiolytics. Antidepressants exhibit efficacy in the management of Generalized Anxiety Disorder (GAD). Imipramine and clomipramine are as effective as second-generation antidepressants that typically cause more side effects than SSRIs or SNRIs (He et al, 2019).

Therefore, they should be tried before utilizing TCAs. The dosage should be progressively increased to depression therapeutic levels. TCAs can produce deadly toxicity if overdosed, thus suicidal patients should be cautious. All TCAs are readily absorbed and bind to plasma albumin with 90–95% affinity at therapeutic plasma concentrations after oral dosing. Their ability to attach to extravascular tissues gives them huge distribution volumes (10-50 l kg1). Plasma concentrations between 50 and 300 ng ml1 (molecular weights 263-314), are considered therapeutic (He et al, 2019).   

Selective serotonin reuptake inhibitors (SSRIs) and selective serotonin-norepinephrine reuptake inhibitors (SNRIs)

 These are first-line drugs due to their favorable benefit-to-risk ratio. Patients should be advised that these antidepressants take 2–4 weeks (sometimes 6 weeks) to reduce anxiety. Adverse effects may worsen in the first two weeks (He et al, 2019). Initial jitteriness or anxiety may reduce treatment compliance. Lowering the antidepressant’s starting dose may reduce negative effects.

Many SSRIs and SNRIs are cytochrome P450 enzyme inhibitors, therefore they may interact with other psychopharmacological drugs and medical treatments. After stopping SSRIs, withdrawal symptoms may occur. These are rarer and less severe than benzodiazepine withdrawal symptoms. These adverse effects may be more common with paroxetine than sertraline or fluoxetine (He et al, 2019).

Buspirone

Buspirone is FDA-approved for treating anxiety and is commonly used in conjunction with SSRIs or SNRIs, particularly for GAD. Only azapirone is approved in the US. According to He, et al (2019) buspirone is found to be less effective than benzodiazepines and antidepressants in the treatment of GAD. Buspirone has a strong first-pass effect and is mostly absorbed orally. A 10 mg dose reaches plasma peak in within an hour. Buspirone is excreted through urine and bile (Rosenthal & Burchum, 2021).

Conclusion

According to Sartori & Singewald (2019), both selective serotonin reuptake inhibitors (SSRIs), such as paroxetine, sertraline, citalopram, and escitalopram and serotonin norepinephrine reuptake inhibitors (SNRIs) like venlafaxine and duloxetine, as well as dopamine norepinephrine reuptake inhibitors such as bupropion are successful therapies for generalized anxiety disorder.

However selective serotonin reuptake inhibitors (SSRIs) are favored over tricyclic antidepressants for depression and anxiety. Antipsychotic drugs such as Quetiapine (Seroquel) also have characteristics that alleviate feelings of anxiety (Rosenthal & Burchum, 2021). 

References

Dragioti, E., Solmi, M., Favaro, A., Fusar-Poli, P., Dazzan, P.,& Thompson, T. (2019). Association of antidepressant use with adverse health outcomes: a systemic umbrella review:JAMA Psychiatry. 76:1241-55. doi:10.1001/jamapsychiarty.2019.2859.

He, H., Xiang, Y., Gao, F., Bai, L., & Fan, Y. (2019. Comparative efficacy and acceptability of fisrst-line drugs for the acute treatment of generalized anxiety diaorder in adults:a network meta-analysis: J Psychiatr Res. 118:21-30. doi:10.2016/j.jpsychires.2019.08.009.

Rosenthal, L. D., & Burchum, J. R. (2021). Lehne’s pharmacotherapeutics for advanced practice nurses and physician assistants (2nd ed.) St. Louis, MO: Elsevier Sartori, S.B., & Singewald, N.(2019). Novel Pharmacological targets in drug development for the treatment of anxiset and anxiety-related disorders: Pharmacol Thel 204:107402. doi:10.1016/j.pharmthera.2019.107402