NURS 6521 Discussion Comparing and Contrasting Pharmacologic Options for the Treatment of Generalized Anxiety Disorder

NURS 6521 Discussion Comparing and Contrasting Pharmacologic Options for the Treatment of Generalized Anxiety Disorder 

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.

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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

 

 

 

Response

This is an in-depth discussion post. Indeed, the treatment of GAD entails both psychotherapy and pharmacotherapy. Essentially, multimodal approaches involving psychotherapy and pharmacotherapy in the management of GAD may distinctively focus on specific symptoms and the inclusion of psychotherapy enhances compliance with treatment and reduces reported adverse effects of pharmacotherapy. Understanding the principles of pharmacokinetics and Pharmacodynamics in the management of GAD is critical in the helping healthcare professionals to make informed decisions about medication formulation and dosage needs (Abuhelwa et al., 2022). It also crucial in building treatment plans entailing medications. The other potential treatment option in this case is psychotherapy. This options involves psychological counseling or talk therapy (Lamb et al., 2019). Here, a patient is expected to work with a therapist to minimize the anxiety symptoms. The popular form of psychotherapy for GAD is cognitive behavioral therapy (CBT). Psychotherapy is CBT aims at teaching particular skills to directly control the patent’s worries and help the patient to slowly return to that had been previously avoided due to anxiety.

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