Antidepressants are pivotal medications in the treatment of depression and anxiety disorders, offering hope and relief to millions worldwide. These medications belong to various sub-classes. Understanding their mechanisms of action, benefits, dosages, and considerations, including their use in hospice care and at the end of life, is crucial for patients, their families, loved ones, and healthcare providers.

Mechanisms of Action:

• Antidepressants work through diversely unique mechanisms, targeting various neurotransmitter systems to alleviate symptoms of depression and anxiety. These medications require weeks to reach therapeutic levels. The most common types include:

1. Selective Serotonin Reuptake Inhibitors (SSRIs): SSRIs like fluoxetine, sertraline, citalopram, escitalopram paroxetine, and fluvoxamine increase the levels of serotonin in the brain by blocking its reabsorption, thereby enhancing mood regulation.

2. Serotonin-Norepinephrine Reuptake Inhibitors (SNRIs): SNRIs such as venlafaxine, desvenlafaxine, levomilnacipran, and duloxetine elevate both serotonin and norepinephrine levels, offering a dual mechanism of action.

3. Tricyclic Antidepressants (TCAs): TCAs are divided into secondary and tertiary amines. TCAs like nortriptyline, amoxapine, desipramine, maprotiline, and protriptyline are secondary amines, while TCAs like amitriptyline, doxepin, clomipramine, imipramine, and trimipramine are tertiary amines. These drugs affect serotonin and norepinephrine reuptake, but they also block other neurotransmitters, contributing to their efficacy.

4. Monoamine Oxidase Inhibitors (MAOIs): MAOIs such as isocarboxazid, phenelzine and tranylcypromine inhibit the enzyme monoamine oxidase, responsible for breaking down neurotransmitters like serotonin, norepinephrine, and dopamine.

5. Atypical Antidepressants: Drugs in this category include the following.

• Bupropion, a dopamine, and norepinephrine reuptake inhibitor.

• Mirtazapine, a tetracyclic antidepressant that works by its central presynaptic alpha-2 adrenergic antagonist effects, resulting in the increase in norepinephrine and serotonin.

• Trazodone, which inhibits serotonin reuptake, blocks H1 and alpha1 adrenergic receptors.

• Nefazodone, which inhibits serotonin and norepinephrine reuptake, and blocks alpha1 adrenergic receptors.

• Vortioxetine, whose exact mechanism of action is unknown, but suggested to selectively inhibit serotonin reuptake, antagonize serotonin 5-HT3 receptors, and agonize serotonin 5-HT1A receptors.

Benefits in Patients with Depression and Anxiety:

Antidepressants offer substantial benefits to individuals struggling with depression and anxiety disorders:

• Alleviation of Symptoms: They help reduce feelings of sadness, hopelessness, and anxiety, improving overall mood and quality of life.

• Prevention of Relapse: Long-term use of antidepressants can help prevent relapse in patients with recurrent depressive episodes.

• Improvement in Functioning: By enhancing mood stability, antidepressants enable individuals to engage more effectively in daily activities and social interactions.

  
  

Dosages:

Dosages of antidepressants vary depending on the medication and individual patient factors. Starting doses are typically low to minimize side effects, with gradual titration based on response.

Drugs that can cause or worsen depression and anxiety.

Side Effects:

Common side effects may include:

• Suicide thoughts and behaviors.

• Serotonin syndrome, especially in combination with other serotonin reuptake inhibitors or MAOIs.

• Increased risk of bleeding, especially when used in combination with anticoagulants, antiplatelet, NSAIDs, other drugs, or supplements that increase the risk of bleeding.

• QT prolongation.

• Nausea.

• Insomnia or sedation.

• Sexual dysfunction.

• Weight changes.

• Dry mouth.

• Constipation.

• Dizziness.

• Withdrawal symptoms when discontinued abruptly. Must taper with discontinuing, except for Fluoxetine because of its long half-life.

It's essential for patients to communicate any side effects to their healthcare provider to adjust the dosage or explore alternative medications.

Use of Antidepressants in Hospice, Palliative care, and at End of Life:

In hospice, palliative care, and end-of-life settings, managing symptoms such as depression and anxiety becomes paramount to enhancing quality of life. Antidepressants can play a crucial role in addressing these psychological distresses.

However, there are considerations unique to this population:

• Limited Timeframe: In end-of-life care, the focus shifts to palliation rather than long-term treatment. Short-acting medications may be preferred over those requiring weeks to reach therapeutic levels.

• Interaction with Other Medications: Prescribers should select antidepressants with care to avoid interactions with other medications commonly used in hospice care, such as opioids and benzodiazepines.

• Tailored Approach: Individualized assessment considering factors like symptom severity, patient preferences, and goals of care is vital. Some patients may benefit from psychotherapy alongside pharmacotherapy.

Effective communication between patients, caregivers, and healthcare providers is key to navigating the complexities of antidepressant therapy and ensuring personalized, holistic care.

 References:

• Practice guideline for the treatment of patients with Major Depressive Disorder, 2010. https://psychiatryonline.org/pb/assets/raw/sitewide/practice_guidelines/guidelines/mdd.pdf (accessed 05/07/2024)

•  VA/DoD Clinical Practice Guideline for the Management of Major Depressive Disorder, 2016 https://www.healthquality.va.gov/guidelines/MH/mdd/MDDCPGClinicianSummaryFINAL1.pdf (accessed 05/07/2024)

dark+linkedin Fidelis Ariguzo - PharmD, RPH | PDC Rx