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

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., & Moralesâ€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.

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 Questionâ€ link, and then select “Create Threadâ€ 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.â€ 

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.â€ 

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 treatmentâ€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.

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 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! 

RUTH

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