Generalized Anxiety Disorder (GAD)

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.

Guidance to Student regarding starting the patient on Tofranil.
It is important that you discontinue the Tofranil due to the client’s bundle branch block. Recall that Tofranil can cause orthostatic hypotension, sudden death, arrhythmias, tachycardia, and QTc prolongation. It should not be used in clients who have already been identified as having an abnormality of cardiac conduction.

The most appropriate course of action for you to take would be the discontinuation of Tofranil and the initiation of an SSRI, such as Paxil (paroxetine) or Zoloft (sertraline), as these are considered first-line agents for the treatment of generalized anxiety disorders. Tofranil is considered a second-line agent.

BuSpar is also considered a second-line agent. It may have a role to play in the care of this client but not until an adequate trial of a first-line agent has been undertaken.

 

  • 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.

BACKGROUND INFORMATION

The client is a 46-year-old white male who works as a welder at a local steel fabrication factory. He presents today after being referred by his PCP after a trip to the emergency room in which he felt he was having a heart attack. He stated that he felt chest tightness, shortness of breath, and a feeling of impending doom. He has some mild hypertension (treated with a low-sodium diet) and is about 15 lbs. overweight. He had his tonsils removed when he was 8 years old, but his medical history since that time has been unremarkable. Myocardial infarction was ruled out in the ER, and his EKG was normal. The remainder of the physical exam was WNL.

He admits that he still has problems with tightness in the chest and episodes of shortness of breath- he now terms these “anxiety attacks.” He will also report occasional feelings of impending doom and the need to “run” or “escape” from wherever he is at.

In your office, he confesses to the occasional use of ETOH to combat worries about work. He admits to consuming about 3-4 beers/per night. Although he is single, he is attempting to care for aging parents in his home. He reports that the management at his place of employment is harsh, and he fears for his job. You administer the HAM-A, which yields a score of 26.

The client has never been on any type of psychotropic medication.

 

MENTAL STATUS EXAM

The client is alert, and oriented to person, place, time, and event. He is appropriately dressed. Speech is clear, coherent, and goal directed. The client’s self-reported mood is “bleh,” and he does endorse feeling “nervous.” The affect is somewhat blunted but does brighten several times throughout the clinical interview. Affect broad. The client denies visual or auditory hallucinations, and no overt delusional or paranoid thought processes are readily apparent. Judgment is grossly intact, as is insight. He denies suicidal or homicidal ideation.

You administer the Hamilton Anxiety Rating Scale (HAM-A), which yields a score of 26.

Diagnosis: Generalized anxiety disorder

 

RESOURCES

§ Hamilton, M. (1959). Hamilton Anxiety Rating Scale. Psyctests, doi:10.1037/t02824-0

 

Decision Point One: Start on Zoloft 50 mg orally daily.

RESULTS OF DECISION POINT ONE

  •  Client returns to the clinic in four weeks
  •  Client informs you that he has no tightness in chest or shortness of breath
  •  Client states that he noticed decreased worries about work over the past 4 or 5 days.
  •  HAM-A score has decreased to 18 (partial response)

 

Decision Point Two: Increased dose to 75 mg orally daily

RESULTS OF DECISION POINT TWO

  •  Client returns to clinic in four weeks
  •  Client reports an even further reduction in his symptoms
  •  HAM-A score has now decreased to 10. At this point- continue current dose (61% reduction in symptoms)

 

Decision Point Three: Maintain current dose

RESULTS OF DECISION POINT THREE
At this point, it may be appropriate to continue the client at the current dose. It is clear that the client has a good response (as evidenced by greater than a 50% reduction in symptoms), and the client is currently not experiencing any side effects, and the current dose can be maintained for 12 weeks to evaluate the full effect of the drug. Increasing drugs at this point may yield a further decrease in symptoms but may also increase the risk of side effects. This is a decision that you should discuss with the client. Nothing in the client’s case tells us that we should consider adding an augmentation agent at this point, as the client is demonstrating a response to the drug. Avoid polypharmacy unless symptoms cannot be managed by a single drug.

 

Answer

Generalized Anxiety Disorder

According to the National Comorbidity Survey Replication (NCS-R), Anxiety disorders are the most common type of psychiatric disorder in the United States, with a lifetime prevalence of approximately 32% (Garakani et al., 2020). Globally, the World Health Organization reports that approximately 264 million people suffer from anxiety disorders, indicating a 15% increase since 2005 (Garakani et al., 2020). Due to their high prevalence, anxiety disorders can lead to missed school and workdays and impose a greater economic burden than other psychiatric disorders. This paper analyzes the medication regimen of a patient presenting with Generalized Anxiety Disorder.

A 46-year-old male welder presents with chest tightness, shortness of breath, and a feeling of impending doom. He reports occasional episodes of shortness of breath and chest tightness, which he now terms anxiety attacks, along with occasional feelings of impending doom. He admits to using alcohol to cope with worries about work and reports caring for aging parents. The HAM-A score is 26, indicating severe generalized anxiety disorder.

Decision Point One: Start on Zoloft 50 mg orally daily.

In the case scenario, the patient presents with symptoms of chest tightness, shortness of breath, and feelings of impending doom. He has been to the emergency room as he suspected a heart attack, which was ruled out. He reported occasional alcohol use and worries about work. The Hamilton Anxiety Rating Scale (HAM-A) score was 26, indicating moderate to severe anxiety.

Starting the client on Zoloft 50 mg orally daily is the right decision since sertraline is a first-line anxiolytic. Zoloft, a selective serotonin reuptake inhibitor (SSRI) medication, is effective in treating symptoms of generalized anxiety disorder. The recommended starting dose for Zoloft is 50 mg per day, according to Singh and Saadabadi (2019). Using the client’s HAM-A score of 26 concludes severe anxiety, thus, medication is necessary to manage his symptoms. Zoloft is proven to be effective in treating anxiety and is generally well-tolerated. The client has no history of psychotropic medication use; therefore, starting with a low dose is recommended. When the client returns to the clinic four weeks after starting Zoloft 50mg, he should report that he no longer experiences chest tightness or shortness of breath, indicating that the medication has alleviated the client’s anxiety symptoms. The client will report feeling more relaxed, less irritable, and ability to focus better. The client’s report of decreased worry about work over the past 4 or 5 days shows that the medication is helping to alleviate some of the client’s general anxiety symptoms.

The fact that the client’s HAM-A score has decreased to 18 implies a partial response to the medication. This is because a HAM-A score of 15-23 indicates severe anxiety (Matza et al., 2021). This shows that while the medication has had some effect on the client’s anxiety symptoms, there is still room for improvement. The HAM-A is a standardized assessment tool used to measure the severity of anxiety symptoms, with scores ranging from 0 to 56. A score of 18 indicates that the client’s anxiety symptoms have improved but are still present to some degree. A decrease in the HAM-A score does not necessarily mean that the client’s anxiety is fully under control. The HAM-A score is just one tool used to assess anxiety symptoms, and it is important also to consider the client’s self-report of symptoms and overall functioning. While a decrease in the HAM-A score is a positive sign, it is crucial to continue to monitor the client’s response to the medication and make adjustments as necessary to achieve the best possible outcome.

Decision Point Two: Increased Dose To 75 Mg Orally Daily

After reviewing the client a second time, increasing the client’s Zoloft dosage from 50mg to 75mg orally daily is considered. The decision to increase the dosage is based on the client’s partial response to the medication, as indicated by a decrease in HAM-A score to 18 and the continued presence of some anxiety symptoms. According to the current evidence-based practice guidelines for the treatment of generalized anxiety disorder, Zoloft is a first-line medication option, with a recommended starting dose of 50mg daily, which can be increased to a maximum dose of 200mg daily (Singh & Saadabadi, 2019). The recommended dosage range for most patients is between 50mg and 150mg daily, depending on individual patient factors and response to treatment in reference to the HAM-A score.

Increasing the dosage of Zoloft will result in further reduction of the client’s anxiety symptoms, including symptoms of worry and feelings of impending doom. However, it is important to consider the potential side effects associated with increasing the dosage. Common side effects of Zoloft include nausea, diarrhea, dizziness, headache, insomnia, and decreased libido (Quagliato et al., 2019). Of importance, the client is 46 years old and not married. It is also important to inquire whether the client plans on getting married at some point and having children before further increasing the dosage. Additionally, the client should be informed of these potential side effects and advised to report any new or worsening symptoms to the healthcare provider.

As a healthcare provider, it is also important to put into consideration that medication alone might not be sufficient in the treatment of generalized anxiety disorder. Bandelow et al. (2022) state that cognitive-behavioral therapy (CBT) is a recommended psychotherapy for the treatment of anxiety disorders, and combination therapy with medication and CBT result in better outcomes than medication alone. The client should be referred to CBT to address their anxiety symptoms and improve overall functioning.

The client returned to the clinic after four weeks and reported an even further reduction in his symptoms, likely due to the increased dosage of Zoloft. The client’s HAM-A score further decrease from 18 to 10, which translates to a 61% reduction in symptoms. This further reduction in anxiety symptoms is an important outcome of the second decision, as it is evidence that Zoloft has been effective in treating generalized anxiety disorder. However, the client did not report any adverse effects, suggesting that the increased dosage was well-tolerated. Finally, the decision to remain at 75mg is maintained.

Decision Point Three: Maintain the Current Dose

The decision to maintain the current dose is due to the fact that the client’s HAM-A score is at 10, which, according to Matza et al. (2021), is mild anxiety. With mild anxiety, a person can go about all their activities of daily living and not display overwhelming symptoms that are debilitating. In line with evidence-based practice guidelines for treating generalized anxiety disorder, which recommend using the antidepressants Zoloft as first-line pharmacotherapy should be maintained once the HAM-A score is below 14 (Forth et al., 2023). Forth et al. (2023) also state that maintenance of the medication dose is necessary to prevent relapse of symptoms.

According to the American Psychiatric Association (APA) practice guidelines for the treatment of patients with generalized anxiety disorder, it recommends the continuation an effective medication at a therapeutic dose for at least 6-12 months to prevent relapse and consolidate the gains made during acute treatment (Sørensen et al., 2022). Furthermore, increasing the dose of Zoloft at this point is unnecessary since the client has already shown a good response to Zoloft 75mg, with a greater than 50% reduction in symptoms and a decrease in HAM-A score from 26 to 10. According to a meta-analysis of 15 randomized controlled trials, increasing the dose of SSRIs beyond the standard recommended dose for depression and anxiety disorders did not result in a statistically significant improvement in symptom reduction (Rink et al., 2022).

Maintaining the current dose also aids in minimizing the risk of potential side effects associated with higher doses of Zoloft, such as gastrointestinal disturbances, sexual dysfunction, and serotonin syndrome. The decision to continue at the current dose should be made in collaboration with the client, taking into consideration their individual needs, preferences, and response to treatment. Of importance to note is that the maintenance of the current dose of Zoloft is to be monitored regularly, with regular follow-up appointments to assess the client’s symptoms and any side effects. If the client’s symptoms worsen or adverse effects develop, the medication regimen should be adjusted or changed.

Personalized Plan Of Care

Medication management: As shown by the case study, the patient has had a positive response to selective serotonin reuptake inhibitors (SSRIs) such as Zoloft. Therefore, continuing the current dose is appropriate for the patient. However, if there is a lack of response or significant side effects, other SSRI options or other medication classes, such as benzodiazepines or pregabalin, could be considered, such as Buspirone. It is important to note that buspirone has a slow onset and could take up to 2 weeks to achieve a maximum therapeutic effect, with presenting side effects such as dizziness, nausea, headache, and nervousness. It is crucial to monitor the patient for these side effects and adjust the dose if necessary especially considering that he works as a welder. Additionally, Buspirone can interact with monoamine oxidase inhibitors (MAOIs), which can lead to an increase in blood pressure (Jones & Husain, 2021). Reviewing the patient’s medication history and checking for potential drug interactions before starting treatment with buspirone is important. It is essential to monitor the patient’s response and adjust medication accordingly.

References

Bandelow, B., Werner, A. M., Kopp, I., Rudolf, S., Wiltink, J., & Beutel, M. E. (2022). The German Guidelines for the Treatment of anxiety disorders: first revision. European Archives of Psychiatry and Clinical Neuroscience272(4), 571–582. https://doi.org/10.1007/s00406-021-01324-1

Forth, E., Buehner, B., Storer, A., Sgarbossa, C., Milev, R., & Chinna Meyyappan, A. (2023). A systematic review of probiotics as an adjuvant treatment for psychiatric disorders. Frontiers in Behavioral Neuroscience17, 1111349. https://doi.org/10.3389/fnbeh.2023.1111349

Garakani, A., Murrough, J. W., Freire, R. C., Thom, R. P., Larkin, K., Buono, F. D., & Iosifescu, D. V. (2020). Pharmacotherapy of anxiety disorders: Current and emerging treatment options. Frontiers in Psychiatry11, 595584. https://doi.org/10.3389/fpsyt.2020.595584

Jones, B. D. M., & Husain, M. I. (2021). Tranquilizer/Anxiolytics: Buspirone. In NeuroPsychopharmacotherapy (pp. 1–10). Springer International Publishing. https://doi.org/10.1007/978-3-319-56015-1_160-1

Matza, L., Morlock, R., Sexton, C., Malley, K., & Feltner, D. (2021). Identifying HAM-A cutoffs for mild, moderate, and severe generalized anxiety disorder. International Journal of Methods in Psychiatric Research. Researchgate.net. https://doi.org/19.223-32.10.1002/mpr.323.

Quagliato, L. A., Cosci, F., Shader, R. I., Silberman, E. K., Starcevic, V., Balon, R., Dubovsky, S. L., Salzman, C., Krystal, J. H., Weintraub, S. J., Freire, R. C., Nardi, A. E., & International Task Force on Benzodiazepines. (2019). Selective serotonin reuptake inhibitors and benzodiazepines in panic disorder: A meta-analysis of common side effects in acute treatment. Journal of Psychopharmacology (Oxford, England)33(11), 1340–1351. https://doi.org/10.1177/0269881119859372

Rink, L., Adams, A., Braun, C., Bschor, T., Kuhr, K., & Baethge, C. (2022). Dose-response relationship in selective serotonin and norepinephrine reuptake inhibitors in the treatment of major depressive disorder: A meta-analysis and network meta-analysis of randomized controlled trials. Psychotherapy and Psychosomatics91(2), 84–93. https://doi.org/10.1159/000520554

Singh, H. K., & Saadabadi, A. (2019). Sertraline. Europepmc.org. https://europepmc.org/article/nbk/nbk547689

Sørensen, A., Juhl Jørgensen, K., & Munkholm, K. (2022). Clinical practice guideline recommendations on tapering and discontinuing antidepressants for depression: a systematic review. Therapeutic Advances in Psychopharmacology12, 20451253211067656. https://doi.org/10.1177/20451253211067656

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