Treating Depression and Alcohol Use Disorder With Integrated Pharmacotherapy

Introduction and Diagnosis

Alcohol abuse is regarded as one of the most significant contributing factors to many mental health illnesses and noncommunicable diseases. A review of the evidence has been conducted to better understand the relationship between alcohol abuse and various mental health conditions such as suicidal ideation, self-harm, depression, and anxiety. The review found a strong link between alcohol abuse and dependence and the aforementioned mental health conditions. However, much remains to be verified regarding the nature and causality of these links. The coexistence of alcohol dependence or abuse and mental health illnesses significantly affects the course and outcomes of those conditions. Some studies have shown that treating both alcohol dependence and mental health conditions simultaneously is more beneficial than focusing on mental health conditions alone.

This paper is a case study involving a 28-year-old woman diagnosed with major depressive disorder and severe alcohol use disorder. The paper describes a psychopharmacological approach to reducing both alcohol use and depressive symptoms, and it presents the implications and outcomes of using a combined treatment strategy.

According to the Diagnostic and Statistical Manual of Mental Disorders (5th edition), alcohol use disorder is characterized by the excessive use of alcohol resulting in at least two of the recognized signs of the disorder. The patient is dependent on alcohol and uses it in a way that causes clinically significant distress or impairment, as characterized by: alcohol frequently being consumed in large volumes; failed efforts to control or reduce consumption; a strong urge or desire to consume alcohol; giving up recreational, social, or occupational activities for alcohol use; and the continued consumption of alcohol despite awareness that it causes mental health problems.

Pharmacological Treatment Approach

The integrated treatment approach has been selected as the treatment of choice. This approach is a combined strategy that has been proven effective for treating comorbid mental health and alcohol use disorders. It involves concurrent but distinct treatment of both the alcohol use disorder and the mental health condition. It frequently incorporates cognitive behavioral therapy (CBT) interventions to improve coping and interpersonal skills and to provide motivation for functional recovery.

Acamprosate is structurally similar to gamma-aminobutyric acid (GABA) and taurine, neurotransmitters that can penetrate the blood-brain barrier. Because of this structural similarity, acamprosate can also penetrate the barrier via acetylation. Its effects in the brain include the antagonization of two receptors—mGluR5 and NMDA—agonism of GABA-A receptors, a reduction in the activity of voltage-dependent calcium channels, and a reduction in the expression of the c-fos gene, which is typically expressed at the onset of alcohol withdrawal. The Food and Drug Administration approved the drug in 2004 for the treatment of alcohol withdrawal syndrome in individuals diagnosed with alcohol use disorder. The standard dose is 666 milligrams administered three times daily. The drug has shown the best outcomes when used in conjunction with detoxification followed by psychotherapy (Guerzoni, Pellesi, Pini, & Caputo, 2018).

Acamprosate is relatively safe in terms of pharmacological interactions. Studies have shown its effectiveness when used together with non-opiate analgesics, sedative-hypnotic drugs, anxiolytics, selective serotonin reuptake inhibitors, and antidepressants. In cases of gastrointestinal side effects such as diarrhea, the initial dose is often reduced to prevent drug-drug interactions. Recent pharmacovigilance data has clearly shown the drug's safety profile: in more than one million cases of usage, no serious adverse events have been reported (Guerzoni et al., 2018).

Acamprosate absorption in the digestive system is typically slow and limited, and the absorption rate varies from person to person. When taken with food, the drug's bioavailability decreases from 42 percent to 23 percent; however, this reduction is not clinically significant, and no dose modification is required. Studies using radioactive C-acamprosate have revealed that the drug is not metabolized by the liver and does not function as an inducer, an inhibitor, or a hepatic enzyme substrate. Its potential for metabolic interaction is therefore low, even in individuals with reduced liver function. The drug does not bind to plasma proteins and has a half-life of more than twenty hours. For these reasons, acamprosate does not produce reciprocal pharmacokinetic interactions with alcohol, naltrexone, disulfiram, oxazepam, imipramine, or diazepam (Guerzoni et al., 2018).

Fluoxetine is a selective serotonin reuptake inhibitor (SSRI). It has demonstrated an antidepressant effect through its interaction with membrane proteins and is widely used to treat panic disorder, bulimia, obsessive-compulsive disorder, and depression. The drug's primary pharmacological effect is the selective inhibition of serotonin (5-hydroxytryptamine; 5-HT) reuptake. Studies have shown this effect to be important in treating OCD, though the precise mechanism remains unclear. Fluoxetine only minimally inhibits other neurotransmitter reuptake and does not exhibit significant affinity for other neurotransmitter sites.

Fluoxetine is an active, selective serotonin reuptake inhibitor, and its active metabolite norfluoxetine shares this effect. Both compounds inhibit other neurotransmitters such as dopamine and noradrenaline only minimally. Fluoxetine's binding affinity for dopaminergic, GABA-benzodiazepine, opioid, serotonergic, histamine H1 and H2, and adrenergic receptors is low. Animal studies have revealed that fluoxetine exposure for more than ten days downregulates terminal and somatodendritic 5-HT autoreceptors. Positron emission tomography (PET) in individuals with OCD has shown enhanced metabolic activity in the cortical, thalamic, limbic, and basal ganglia regions of the brain following fluoxetine use—effects not observed in healthy individuals. It has also been found that fluoxetine normalizes glucose metabolism in the orbitofrontal regions of the brain in individuals with OCD (Fulton & McTavish, 1995).

Oral administration of fluoxetine results in the absorption of approximately 80 percent of the dose in the gastrointestinal tract, with a bioavailability of approximately 77 percent. The drug is a chiral compound, typically sold as a 1:1 mixture of its enantiomers, (S)-fluoxetine and (R)-fluoxetine. Its primary metabolite in the body is norfluoxetine, the demethylated form. Fluoxetine is well-bound to plasma and tissue proteins (approximately 95 percent), which maximizes dose distribution. Steady-state blood plasma concentrations are reached after approximately four to six weeks of administration. The average elimination half-life of fluoxetine is two to seven days, and of norfluoxetine seven to fifteen days, depending on the patient's body weight, age, and renal function. Hepatic impairment significantly affects the clearance of both fluoxetine and its metabolite (Fulton & McTavish, 1995).

Conclusion

Studies have shown that integrated treatment plans for individuals with alcohol use disorder and debilitating psychological illnesses such as bipolar disorder and schizophrenia typically include interventions appropriate to the individual's mental health condition, readiness to engage, motivation, and behavioral skills. Evidence-based practices have shown that strengthening a person's links to social support systems accelerates recovery and generally leads to better outcomes for co-occurring mental health and alcohol use disorders. Cultural competence and sensitivity have also been shown to be important in treatment programs. The most effective comprehensive treatment programs therefore integrate all components of care, including social, educational, pharmacological, and psychological interventions (Yule & Kelly, 2019).

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Yule, A. M., & Kelly, J. F. (2019). Integrating treatment for co-occurring mental health conditions. Alcohol Research: Current Reviews, 40(1).