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1 Short Answer Assessment Major Depressive Disorder (MDD) is a pervasive mental health condition, often compounded by comorbidities such as alcohol abuse. Effective treatment strategies for MDD are critical, particularly when a patient's history includes alcoholism. This analysis delves into the appropriate drug therapy for individuals facing the dual challenge of MDD and alcohol abuse, identifying which drugs are contraindicated and the expected timeline for symptom resolution. Additionally, the analysis explores the predictors of late-onset Generalized Anxiety Disorder (GAD) to shed light on the complexities of GAD diagnosis in older individuals. Furthermore, it investigates potential neurobiological causes of psychotic Major Depression, offering insights into the condition's multifaceted origins. Lastly, the article examines medications across three classes that can induce insomnia, raising awareness about adverse effects and aiding in informed healthcare decisions. Appropriate Drug Therapy for MDD and Alcohol Abuse For a patient with Major Depressive Disorder (MDD) and a history of alcohol abuse, the appropriate drug therapy would involve the use of Selective Serotonin Reuptake Inhibitors (SSRIs), such as Sertraline. SSRIs are considered the first-line treatment for MDD and are also suitable for patients with alcoholism (DeVido & Weiss, 2013). Combining drugs for the treatment of both alcoholism and MDD, such as naltrexone and Sertraline, is an effective approach. Research suggests that the combination can increase the rate of abstinence and improve mood in such a patient. On the other hand, drugs contraindicated for this population include central nervous system (CNS) depressants like Remeron, benzodiazepines, and other CNS depressants. These are contraindicated because they can increase the risk of respiratory depression when combined with alcohol (Stahl, 2021). The timeframe for symptom resolution

2 may vary but typically involves some improvement within four to eight weeks, with complete resolution typically taking a few months depending on finding the right therapeutic drug. Predictors of Late-Onset Generalized Anxiety Disorder  Female Gender. Women are more likely to experience late-onset GAD, potentially due to hormonal changes, social factors, or a higher likelihood of seeking medical help for anxiety symptoms ( Zhao et al., 2020) .  Dementia/Memory Changes: The prevalence of anxiety is notably higher, ranging from 17% to 52%, in individuals with dementia or memory changes (Aggarwal et al., 2017). Individuals with dementia or significant memory changes often face increased anxiety because of the cognitive challenges and uncertainty associated with such conditions.  COPD and Cardiovascular Disease: These conditions have been associated with a greater likelihood of anxiety, with prevalence rates ranging from 13% to 46% (Aggarwal et al., 2017). Persons with Chronic Obstructive Pulmonary Disease (COPD) and Cardiovascular Disease are more susceptible to late-onset GAD due to the physical and psychological stress associated with these chronic health conditions.  Fear of Falling: In older adults, fear of falling can increase anxiety, leading to decreased independence and quality of life. Older adults with a fear of falling may experience heightened anxiety, as this fear impacts their mobility, independence, and overall quality of life, leading to increased worry and anxiety. Potential Neurobiological Causes of Psychotic Major Depression

3  Genetics: While no specific gene has been identified as the sole cause of depression, genetic variations have been associated with a heightened susceptibility to depression ( Dean & Keshavan, 2017) .  Adverse Events in Childhood: Events in childhood can significantly impact the risk of adult depression, as psychosocial events during this period may influence the development of depressive symptoms in adulthood ( Marx et al., 2023) .  Ongoing and Recent Stress: The amount of stress experienced in infancy and childhood can increase an individual's vulnerability to depression in response to later life stressors ( Dean & Keshavan, 2017) .  Environmental Interactions: Dopamine is has been shown to play a pivotal role in the pathophysiology of major depressive disorder. Severe stressors can disrupt the normal inhibitory feedback loop in the brain, leading to an increase in dopamine and altered brain-derived neurotrophic factor levels ( Marx et al., 2023) . Symptoms Required for an Episode of Major Depression An episode of Major Depression, defined as a period lasting at least 2 weeks, requires at least five of the following symptoms as per the DSM-5:  Loss of Interest or Pleasure: Individuals experience a diminished interest or pleasure in activities they usually find enjoyable.  Depressed Mood: This can be self-reported or observed by others. In children, it may manifest as an irritable mood.

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4  Unintentional Weight Loss/Gain or Appetite Changes: A significant weight change of more than 5% in a month or alterations in appetite are indicative (American Psychiatric Association, 2013).  Tiredness, Fatigue, Low Energy: A persistent feeling of tiredness, fatigue, or low energy levels is a common symptom.  Impaired Ability to Think: Difficulties in thinking, concentrating, or making decisions are often observed (American Psychiatric Association, 2013). Classes of Drugs that Precipitate Insomnia There are different classes of drugs that can precipitate insomnia. Examples include:  Alpha Blockers: These drugs can cause insomnia by decreasing REM sleep and potentially leading to daytime sedation. Examples of alpha blockers include Minipress, Alfuzosin, Hytrin, Cardura, and Flomax (Do, 2020).  Beta Blockers: These drugs can cause insomnia by disrupting sleep patterns, resulting in nightmares and frequent awakenings during the night. This effect may be related to their impact on melatonin secretion. Examples include Carvedilol, Atenolol, Propranolol, Metoprolol, Sotalol, and Timolol (Do, 2020).  Corticosteroids: Examples include Methylprednisolone, Cortisone, Triamcinolone, and Prednisone. Corticosteroids can precipitate insomnia by affecting the adrenal glands, leading to a stress response, causing insomnia and nightmares (Do, 2020). Conclusion

5 Understanding the intricacies of mental health conditions and their treatment is crucial for healthcare providers and patients alike. Addressing Major Depressive Disorder (MDD) in individuals with a history of alcohol abuse requires careful consideration of suitable medications while avoiding contraindicated drugs. The predictors of late-onset Generalized Anxiety Disorder shed light on the challenges faced by older individuals, emphasizing the importance of tailored interventions. Investigating the neurobiological underpinnings of psychotic Major Depression offers insight into its origins and potential avenues for more effective treatments. Finally, recognizing medications that can precipitate insomnia highlights the need for informed decision- making in healthcare.

6 References Aggarwal, R., Kunik, M., & Asghar-Ali, A. (2017). Anxiety in later life. Focus , 15 (2), 157-161. https://doi.org/10.1176/appi.focus.20160045 American Psychiatric Association. (2013). Diagnostic and Statistical Manual of Mental Disorders , (5th edn). American Psychiatric Association., https://doi.org/10.1176/appi.books.9780890425596 Dean, J., & Keshavan, M. (2017). The neurobiology of depression: An integrated view. Asian journal of psychiatry , 27 , 101-111. https://doi.org/10.1016/j.ajp.2017.01.025 DeVido, J. J., & Weiss, R. D. (2012). Treatment of the depressed alcoholic patient. Current psychiatry reports , 14 , 610-618. https://doi.org/10.1007/s11920-012-0314-7 Do, D. (2020). Trends in the use of medications with insomnia side effects and the implications for insomnia among US adults. Journal of Sleep Research , 29 (4), e13075. https://doi.org/10.1111/jsr.13075 Marx, W., Penninx, B. W., Solmi, M., Furukawa, T. A., Firth, J., Carvalho, A. F., & Berk, M. (2023). Major depressive disorder. Nature Reviews Disease Primers , 9 (1), 44. DOI: https://doi.org/10.1038/s41572-023-00454-1 Stahl, S. M. (2021). Stahl's essential psychopharmacology: Neuroscientific basis and practical applications (5th Ed.) Cambridge University Press. Zhao, L., Han, G., Zhao, Y., Jin, Y., Ge, T., Yang, W., ... & Li, B. (2020). Gender differences in depression: evidence from genetics. Frontiers in genetics , 11 , 1145. https://doi.org/10.3389/fgene.2020.562316

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