Generalized Anxiety Disorder (GAD) is a condition that can bring a feeling of discomfort and manifests psychologically and physically. Emotional symptoms can be described as fear, dread, and uneasiness. The physical symptoms can be tachycardia, palpitations, trembling, dry mouth, sweating, weakness, fatigue, and shortness of breath. Intervention is necessary when anxiety is crippling and affects normal daily activities. Research shows that alterations in the activity of neurotransmitters such as serotonin, epinephrine, and GABA are factors in GAD. Specifically, a decrease in GABA signaling could lead to hyperexcitability and increased neuronal activity translating to anxiety and symptoms. Other factors include environmental stressors, history of trauma, and genetic predisposition (Burcham & Rosenthal, 2020).
There are several medications that are generally indicated. Selective serotonin reuptake inhibitors (SSRIs), serotonin-norepinephrine reuptake inhibitors (SNRIs), benzodiazepines, buspirone, and pregabalin. SSRIs and SNRIs work by blocking the reuptake of serotonin and or epinephrine into the presynaptic cleft. This allows more of these neurotransmitters to be available to do their work. Serotonin interacts with GABA by modulating its receptor function. By increasing GABA-A receptor activity, serotonin can enhance the inhibitory effects of GABA, leading to an overall decrease in neuronal excitability and a reduction in anxiety and other symptoms (Marasine et al., 2021).
Reflecting on my clinical experience reminds me of a 38-year-old African American woman prescribed with Cymbalta (generic duloxetine) for GAD. She had a history of schizoaffective disorder as well as multiple substance use (alcohol, methamphetamines, opiates) Type 2 diabetes, and likes to take ibuprofen daily for headaches. Based on this case study it is advisable to monitor for abnormal bleeding when taking SNRIs with aspirin, nonsteroidal anti-inflammatory drugs, or anticoagulants like warfarin. It should also be used cautiously in patients with a history of mania and may worsen glycemic control in diabetics. No dose greater than 60 confers additional benefits. At the maximum recommended dose, I would advise her to monitor for side effects such as nausea, dry mouth, constipation, drowsiness, and dizziness. Classified as an SNRI, it is approved by the FDA for GAD, major depressive disorder, fibromyalgia, and chronic musculoskeletal pain. It works by increasing the levels of serotonin and norepinephrine in the brain. Norepinephrine can bind to both alpha- and beta-adrenergic receptors in the brain, which can have different effects on neuronal activity. Activation of alpha-2 adrenergic receptors can decrease neuronal excitability and promote calmness (Montgomery, 2006).
Benzodiazepines are mostly used for short-term stabilization of GAD as it has the potential for abuse. GABA is the main inhibitory neurotransmitter in the central nervous system which plays a major role in reducing anxiety and promotes calmness. When benzodiazepines bind to the GABA-A receptor, they increase the affinity of the receptor for GABA, which leads to increased chloride ion influx into the neuron. This influx of chloride ions hyperpolarizes the neuron, making it less excitable and reducing the likelihood of an action potential (Gielen et.al, 2012).
References
Burchum, J., Rosenthal, L. D. (2020, February). Lehne’s Pharmacotherapeutics for Advanced Practice Nurses and Physician Assistants, 2nd Edition. [[VitalSource Bookshelf version]]. Retrieved from vbk://9780323554954
Gielen, M. C., Lumb, M. J., & Smart, T. G. (2012). Benzodiazepines modulate GABAA receptors by regulating the preactivation step after GABA binding. The Journal of Neuroscience: The Official Journal of the Society for Neuroscience, 32(17), 5707–5715. https://doi.org/10.1523/JNEUROSCI.5663-11.2012Links to an external site.
Marasine, N. R., Sankhi, S., Lamichhane, R., Marasini, N. R., & Dangi, N. B. (2021). Use of antidepressants among patients diagnosed with depression: A scoping review. BioMed Research International, 202 6699028. https://doi.org/10.1155/2021/6699028
Montgomery, S. (2006). Serotonin noradrenaline reuptake inhibitors: Logical evolution of antidepressant development. International Journal of Psychiatry in Clinical Practice, 10, 5–11. https://doi.org/10.1080/13651500600637049Links to an external site.
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