Multiple Mental Health Disorders Paper

Appropriate Drug Therapy for Major Depressive Disorders, MDD.

Arguably, there is an association between alcohol use and depressive illnesses, one that often results into poor health outcomes. The assessment and treatment of patients with depression cooccurring with alcohol use has many challenges. When considering treatment of such patients, several approaches have been proposed with each having both its advantages and disadvantages. The FDA approves the use of selective serotonin reuptake inhibitors (SSRIs) as first-line agents for the treatment of depressive illnesses (American Psychiatric Association, 2013).

SSRIs are tolerated better and are safer in MDD patients who have a history of alcohol use. Sertraline is an example of an SSRI used for the management of MDD. Studies have shown that patients, especially those with severe symptoms, benefit the most from sertraline. The recommended dose of sertraline is a maximum of 200 mg/d.  SSRIs can also be combined with drugs used for the treatment of alcohol dependance such as Naltrexone (Gasparyan, 2021).

A study by McHugh & Weiss (2019) concluded that a combination of sertraline and naltrexone produced a more desired effect of reduced depressive symptoms and a longer delay before relapse of alcohol use. Combination therapy of both drugs yielded a longer relief when compared to single-medication. It is generally not advised to take SSRIs concurrently with alcohol as this may worsen the symptoms of depression. Also, it increases the risk of overdose, thereby increasing the chances of occurrence of such side effects as drowsiness and dizziness. It should take around 4- 6 weeks before the effects of treatment can be appreciated (McHugh & Weiss, 2019).

Predictors of Late Onset Generalized Anxiety Disorder

Within the health sector, anxiety disorders remain largely underrecognized despite their immense contribution to mental and physical disability among geriatric patients. In fact, being a chronic disorder, generalized anxiety disorder (GAD) has direct association with increased disability and suicide attempts. GAD is a multifactorial disorder and usually precedes major depression, and if often characterized by high stress levels. Among the risk factors for GAD draw from both proximal and distal factors, some of which can be modifiable by healthcare intervention.

Noteworthy though is that treatment of GAD is not easy, hence the need for early identification of the predictors of the disease among elderly patients. Aging is may be associated with psychosocial risk factors such as physical illness and disability. Aging also can be protective against anxiety due to the development of better coping strategies over the years changes in life perspectives which render certain anxiety triggers as less provoking. Principle predictors of late onset GAD are therefore:

  • Alterations in the hypothalamic pituitary adrenal (HPA) axis may interfere with stress resilience and thus be a potential mediator of anxiety and mood disorders.
  • Being female. Female specific social and biological factors tend to affect the course of anxiety disorders. Estradiol has been implicated in the pathogenesis of anxiety as it “modulates fear learning and fear extinction,” (Hellwig & Domschke, 2019).
  • Recent adverse life events. Adverse events may expose one to massive trauma which might interfere with their subsequent coping mechanisms. This leaves one always weary and on the lookout and this can be severe to the extent that it becomes pathological. With increasing age, the risk of experiencing losses, such as death of a spouse, increases. This impedes maintenance of relationships and subsequent loneliness. Loneliness has been linked to the development of anxiety.
  • Having a chronic physical and mental disorder. These disorders include depression, phobias, dyslipidemia, heart failure, respiratory disorders.
  • Past medical history of GAD
  • Parental loss and low affective support, especially in childhood.
  • History of mental illness in the family such as in the parents.
  • Poverty

Potential Neurobiology Causes of Psychotic Major Depression

As a mood disorder, MDD presenting with psychotic features has been associated with substantial morbidity and mortality. Structural and functional abnormalities of the brain are associated with MDD. Some of the potential neurobiology causes implicated in the pathogenesis of psychotic major depression are:

  • The glutamatergic hypothesis. This explains how glutamate-mediated toxicity plays a role in the development of psychosis. Elevated glutamatergic neurotransmission has been implicated in the pathogenesis of schizophrenia. Glutamate neurotoxicity (GNT) is damage of cell components which leads to cell death (Olloquequi et al., 2018).
  • Dopamine is thought to play a major role in the pathogenesis of MDD. Environmental threats increase the levels of dopamine in the brain. Local inhibitory feedback mechanisms kick in to return the dopamine levels to desired levels and achieve homeostasis. Severe stressors however disrupt this feedback mechanism by altering the striatal levels of brain-derived neurotrophic factor therefore resulting in an abnormal striatal dopamine system feedback (Hellwig & Domschke, 2019).
  • Alterations in the hypothalamic pituitary adrenal (HPA) axis may interfere with an individual’s resilience to stress, thus predisposing them to anxiety and mood disorders. Abnormal function of the HPA axis also play a role in the development of MDD. The HPA system is directly activated by stress. The hypothalamus produces corticotropin-releasing factor which results in the release of corticotropin in the pituitary. Corticotropin stimulates the adrenal glands to release cortisol which is the stress hormone. Glucocorticoid receptors in the hippocampus are sensitive to cortisol and this helps the hippocampus to regulates the HPA axis. Chronic stress causes a downregulation of the glucocorticoid and corticotropin -releasing factor receptors and increases their respective agonists. These changes result in chronic disinhibition of the HPA axis (Hellwig & Domschke, 2019)
  • In a study conducted by Croarkin (2018), a reduced hypothalamic and subgenual cortex connectivity was noted in patients with psychotic depression. This was noted on a resting-state functional MRI scan. Structural imaging studies also reveal a reduction in the size of the hippocampi in MDD patients. Overall, neuroimaging studies indicate general brain atrophy in MDD patients. Abnormalities in the interconnectivity of subcortical and cortical regions of the brain have also been noted.

Five Symptoms of An Episode of Major Depression

The DSM-5 (2013) outlines an episode of major depression as lasting at least 2 weeks with one or more symptoms of depressions. At least one of the symptoms should be a depressed mood or anhedonia (loss of pleasure). Other symptoms associated with major depression are:

  • Fatigue or loss of energy occurring for the better part of the day, almost every day.
  • Diminished interest in activities occurring for the better part of the day, almost everyday
  • Depressed mood occurring for the better part of the duration
  • Diminished concentration and indecisiveness.
  • Recurrent suicidal ideations

Classes of Drugs that Precipitate Insomnia

Insomnia is a sleep disorder that can result in unrefreshing and non-restorative sleep. Various medication can precipitate the onset of this disorder. Some of these drug-classes include;

  • Alpha-blockers. These drugs are used for the treatment of conditions such as hypertension and benign prostatic hyperplasia (BPH). They inhibit the action of vasoconstrictors such as noradrenaline therefore producing a vasodilatory effect. An example is prazosin. These drugs cause insomnia by decreasing REM sleep especially in the elderly (Neel, 2021).
  • Selective serotonin-reuptake inhibitors (SSRIs) which are used to treat symptoms of moderate to severe depression. They act by blocking the reuptake of serotonin in the brain. An example of SSRI is Fluoxetine. SSRIs cause agitation which can lead to sleep insomnia deprivation
  • These drugs are used as anti-inflammatory agents. They are used to treat rheumatoid arthritis and inflammation of muscles and blood vessels. An example of a corticosteroid is Prednisone. Corticosteroids cause insomnia by stimulating the adrenal glands to release cortisol, the stress hormone. The body presumes that it’s under stress and therefore will stay awake and one becomes unable to sleep and relax (Neel, 2021).

References

  • American Psychiatric Association. (2013). Diagnostic and Statistical Manual of Mental Disorders. 5th ed. Diagnostic and Statistical Manual of Mental Disorders (DSM–5). DSM-5. Accessed from https://www.psychiatry.org/psychiatrists/practice/dsm.
  • Croarkin, P. E. (2018). Indexing the neurobiology of psychotic depression with resting state connectivity: Insights from the STOP-PD study. Ebiomedicine, 37, 32–33. Https://doi.org/10.1016/j.ebiom.2018.10.010
  • Gasparyan, A., Navarrete, F., & Manzanares, J. (2021). The administration of sertraline plus naltrexone reduces ethanol consumption and motivation in a long-lasting animal model of post-traumatic stress disorder. Neuropharmacology, 189(), 108552. https://doi.org/10.1016/j.neuropharm.2021.108552
  • Hellwig, S., & Domschke, K. (2019). Anxiety in Late Life: An Update on Pathomechanisms. Gerontology, 65,465-473. Doi: 10.1159/000500306
  • McHugh, R. K., & Weiss, R. D. (2019). Alcohol Use Disorder and Depressive Disorders. Alcohol research: current reviews, 40(1). https://doi.org/10.35946/arcr.v40.1.01
  • Neel, A. B. (2021). Insomnia – 10 medications that can cause sleeplessness. Retrieved from https://www.aarp.org/health/drugs-supplements/info-04-2013/medications-that-can-cause-insomnia.html.
  • Olloquequi, J., Cornejo-Córdova, E., Verdaguer, E., Soriano, F. X., Binvignat, O., Auladell, C., & Camins, A. (2018). Excitotoxicity in the pathogenesis of neurological and psychiatric disorders: Therapeutic implications. Journal of Psychopharmacology, 32(3), 265–275. https://doi.org/10.1177/0269881118754680