Module 3: Discussion– Anxiety & Sleep – Discussion Board Replies

Post 1: 

  1. Alpha-2-delta ligands are sometimes used to treat anxiety. Give at least two examples and explain their mechanism of action (when treating anxiety).

Stahl (2021) illustrated that two core components of anxiety are fear and worry. Fear is caused by overactivation of neurotransmission in amygdala and worry is caused by overactivation of neurotransmission in the cortico-striato-thalamocortical (CSTC) loops (p. 366). In order to treat anxiety, pharmacological interventions must target amygdala and CSTC pathways by blocking neurotransmission in voltage-sensitive calcium channels. Alpha-2-delta ligands are known for binding to the subunits of VSCCs including presynaptic N and P/Q VSCCs to decrease glutamate release. Two examples such as pregabalin and gabapentin are alpha-2-ligands to treat anxiety. Hong et al. (2021) also illustrated that medications like gabapentin and pregabalin have inhibitory properties by decreasing alpha-2-delta and alpha-1 on cell surface and voltage currents.

  1. What is serotonin’s role in anxiety? How do antidepressants hypothetically treat anxiety? (You may need to revisit Chapter 7)

Stahl (2021) brought up an interesting point that since major depressive disorder and anxiety disorders share common symptoms such as fatigue, sleeping problems, and concentration, pharmacological treatments for both disorders which are symptom-based, or brain circuit focused can also be similar. Stahl (2021) also indicated that first-line treatments for anxiety were designed to treat depression (p.368). The main neurotransmitter serotonin that is responsible for depression also interacts with amygdala and the cortico-striato-thalamocortical (CSTC) loops region that cause fear and worry. Therefore, selective serotonin reuptake inhibitors (SSRIs) and serotonin-norepinephrine reuptake inhibitors (SNRIs) can treat anxiety disorders by increasing serotonin level in the amygdala and the CSTC loops by blocking the serotonin transporter also known as SERT. Stahl (2021) also mentioned that medications for treating depression such as a serotonin 1a partial agonist like buspirone or serotonin partial agonist reuptake inhibitors (SPARs) are designed to treat anxiety as well due to the serotonin role in treating anxiety.

  1. Antihistamines are frequently used in anxiety and to aid with sleep. Explain the properties they have that make them effective. What are the potential side effects?

Stahl (2021) emphasized the importance of histamine role in the sleep wake cycle that when histamine binds with H1 receptors, it activates the G-protein that leads to activation of phosphatidylinositol and the transcription factor which in turn result in responses such as “wakefulness, normal alertness, and pro-cognitive actions” (p. 402). Stahl (2021) also stated that histamine is produced in the brain region called tuberomammillary nucleus and it travels to different brain regions to promote wakefulness and treat anxiety. However, excessive histamine can lead to patients experiencing the other end of the spectrum which is panic, fear or even hallucinations and psychosis. The most common and potential side effect of antihistamines is sedation due to its anticholinergic properties.



Hong, J. S. W., Atkinson, L. Z., Al‐Juffali, N., Awad, A., Geddes, J., Tunbridge, E. M., Harrison, P. J., & Cipriani, A. (2021). Gabapentin and pregabalin in bipolar disorder, anxiety states, and insomnia: Systematic review, meta-analysis, and rationale. Molecular Psychiatry, 27(3), 1339–1349.

Links to an external site.

Stahl, S. M. (2021). Stahl’s Essential Psychopharmacology: Neuroscientific Basis and Practical Applications. Cambridge University Press.

Post 2:

  1. What is considered first-line treatment in regard to pharmacotherapy for Generalized Anxiety Disorder? What is second line? (You may need to research this, please cite your source).

Per Strawn et al (2018), in adults with Generalized Anxiety Disorder (GAD), SSRIs and SNRIs (Prozac, Cymbalta, Zoloft) represent the first-line psychopharmacologic treatment while second-line pharmacotherapies may include buspirone, benzodiazepines, SGAs and pregabalin. In pediatric patients with GAD, SSRIs should be considered the first line pharmacotherapy and psychotherapy enhances antidepressant response (para.3).

  1. Explain the impact half-lives have on agent’s tolerability and efficacy. For this discussion, concentrate on Z-drugs.

Stahl (2021) describes the “Goldilocks solution” for guidance on prescribing Z-drugs for insomnia. In the Goldilocks solution, the onset to achieving threshold and the duration of time above the sleep threshold are important factors in efficacy. Ultra-long half lives (T1/2) hypnotics (Flurazepam and Quazepam) can cause drug accumulation which can lead to toxicity especially in the elderly. In addition, Z-drugs with long T1/2 (ProSom, Restoril, Remeron) may not wear off until after the patient awakens, leading to a “hangover-like” effect. Drugs with long T1/2 are considered “way too hot” like Goldilocks’ porridge. This can lead to a decrease in medication adherence. Therapeutic doses of Z-drugs with long half-lives may need a lower dose or to be administered earlier.

Contrarily, Z-drugs with short T1/2 (Ambien, Halcion, Melatonin) wear off too quickly, before time to awake. This can lead to patients taking more medication than prescribed to achieve results. Thus, these Z-drugs are considered “too cold”, and the dosing may need to be increased, admin may need to be later, or the mechanism may need changed to achieve therapeutic results (p.428).

  1. Which benzodiazepines are approved for insomnia? Are they considered first line agents in the treatment of insomnia?

Asnis et al (2016) state the FDA approved benzodiazepines use as hypnotics in 2005, but benzodiazepines have been used “off label” for decades in the treatment of insomnia (para.1). Per Stahl (2021), there are currently 5 benzodiazepines (Dalmane, Doral, Halcion, ProSom and Restoril) that are approved by the FDA in the treatment of insomnia (p.421).

However, benzos are not usually the “first line” treatment, instead they’re considered second-line agents for insomnia d/t problems such as loss of efficacy overtime (tolerance), withdrawal, and rebound insomnia. If first-line treatments fail to work, benzos are helpful in treatment-resistant insomnia (p.422).


Asnis, G. M., Thomas, M., & Henderson, M. A. (2015). Pharmacotherapy Treatment Options for Insomnia: A Primer for Clinicians. International journal of molecular sciences17(1), 50.

Links to an external site.

Stahl, S.M. (2021). Stahl’s essential psychopharmacology: neuroscientific basis and practical applications. 5th ed-ebook. Cambridge University press.

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 pharmacotherapy19(10), 1057–1070.

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