Posted: January 16th, 2024

Linda is a 49-year-old female with a history of depression

Linda is a 49-year-old female with a history of depression. She reports that she is suffering from fatigue, tearfulness, and difficulty sleeping. She has been taking fluoxetine 20mg for the past six months. What changes, if any, would you make to her plan of care and why?

Prescriber’s Guide
Antidepressants – https://online.vitalsource.com/reader/books/978110…
Stahl’s Essential Psychopharmacology
Chapter 7 – https://online.vitalsource.com/reader/books/978113…

Linda has been taking fluoxetine 20mg for 6 months for depression. While this is generally a good starting dose, some individuals require a higher dose to achieve an adequate therapeutic response (Stahl’s Essential Psychopharmacology, Chapter 7). Given Linda’s ongoing symptoms of fatigue, tearfulness and difficulty sleeping, increasing her fluoxetine dose could be beneficial. The prescribing information for fluoxetine indicates a target dose of 20-60mg per day (Prescriber’s Guide to Antidepressants).
Gradually increasing the dose over the next 4-6 weeks, with follow up to assess response and tolerability, would be reasonable. Most individuals achieve maximal benefit from SSRIs like fluoxetine between 8-12 weeks of treatment at an adequate dose (Prescriber’s Guide to Antidepressants). If increasing the dose does not improve Linda’s symptoms after 6-8 more weeks, it may be time to consider an alternative antidepressant medication.
Continuing cognitive-behavioral therapy (CBT) or interpersonal therapy (IPT) while optimizing her antidepressant medication could also help Linda’s depression. Psychotherapy has been shown to enhance antidepressant treatment outcomes (Stahl’s Essential Psychopharmacology, Chapter 7). Ensuring she has social and family support during this time is also important.
With dose optimization and/or a change in antidepressant if needed, along with continued psychotherapy and social support, Linda’s depression symptoms have a good chance of remitting over the next 2-3 months. Regular follow up will allow her provider to monitor her progress and make any additional adjustments to her plan of care as required. Please let me know if you have any other questions!
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Antidepressants
Section 2 of 3
In the treatment of depression, symptoms reduction at 50 percent is considered a response to treatment. The goal is complete remission of symptoms; however, this can be difficult to reach at times and typically not reached with the first antidepressant medication choice. Common causes of lack of remission include sleep disturbances, tiredness, amotivation, anhedonia, and somatic complaints. Adults are most likely to benefit from antidepressant use.

Click below to learn more about each class of antidepressants.
SSRIs
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All SSRIs work by inhibiting the serotonin transporter. Most blockage occurs in the midbrain rather than at the termination of the axons. Desensitization occurs first at the presynaptic auto receptors. This causes a build up at the synapses, thus causing postsynaptic serotonin receptors to desensitize as well. In large clinical studies, there are minimal differences in effectiveness of different SSRIs. 5HT2C antagonism is generally activating and helps to decrease fatigue, which can be positive but also negative if the patient has extreme anxiety, agitation, or sleep problems. Paroxetine, escitalopram, citalopram, and sertraline are all SSRIs.

SPARIs
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Vilazodone is the medication in this class. SPARIs combine the action of SSRIs with 5HT1A partial agonism. This combination was previous achieved by adding on an antipsychotic or buspirone to an SSRI or SNRI.

SNRIs
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SNRIs combine SERT inhibition with different levels of norepinephrine transporter inhibition. Thought to have two actions, SNRIs also affect dopamine in the prefrontal cortex. Milnacipran is the most potent inhibitor of the norepinephrine transporter. Venlafaxine is a commonly prescribed SNRI. The XR version helps to decrease side effects and decreases the number of doses needed daily. Other SNRIs include duloxetine and desvenlafaxine. This class can also be used for chronic pain.

NDRIs
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Bupropion is the only medication in this class. It is believed that this medication blocks the reuptake of norepinephrine and dopamine. Three formulations are available for immediate release, twice a day dosing (SR), and once a day dosing (XL). This medication has been used for depression, ADHD, and smoking cessation.

MAOIs
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MAOIs are considered classic antidepressants. This class cannot be mixed with several other psychiatric medications. Because of this, they are not often used and require a wash-out period between their use and use of other antidepressants. Phenelzine, tranylcypromine, and isocarboxazid are all irreversible enzyme inhibitors. This class of medication requires some dietary restrictions as well. Foods that should be avoided when taking these medications include the following: tap and unpasteurized beer, aged cheeses, banana peel, soy/tofu, sauerkraut, kimchee, or dried, aged, smoked, fermented, spoiled or improperly stored meat, poultry or fish. Selegiline is a selective MAO-B inhibitor at low oral doses; administering low oral doses of selegiline does not have any dietary restrictions but also does not inhibit MAO-A in the brain and is therefore not an antidepressant. At high oral doses, selegiline does inhibit MAO-A and therefore has antidepressant effects but requires the need to restrict dietary tyramine.

Tricyclics
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Tricyclics are also considered classic antidepressants. This drug class blocks serotonin and norepinephrine reuptake. Clomipramine has a greater affinity to block serotonin while desipramine, maprotiline, nortriptyline, and protriptyline block norepinephrine more. They all block both to some extent.

SARIs
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The prototype drug that blocks serotonin 2A and 2C (5HT2A and 5HT2C) receptors as well as serotonin reuptake is trazodone, classified as a serotonin antagonist/reuptake inhibitor (SARI), or, more fully, as a serotonin 2A/2C antagonist and serotonin reuptake inhibitor. Nefazodone is another SARI with robust 5HT2A antagonist actions and weaker 5HT2C antagonist and SERT inhibition but is no longer commonly used because of rare liver toxicity. Trazodone dosing effects how this medication works. Trazodone is often used with other SSRIs to help with insomnia.

L-5 Methyfolate can be used to augment antidepressants. It is believed that this form of folate effects monoamine levels. Genetic variations can affect L-methylfolate level.

One can consider symptoms in the selection of antidepressants. Concentration and fatigue is thought to be related to norepinephrine and dopamine. The medications most effective for this are NDRIs, NRIs, SNRIs, MAOIs. Sleep disturbance may benefit from sedating antidepressants like mirtazapine and trazodone. Pain with depression may be best treated with SRNIs. Sexual dysfunction can be treated with NDRI, SARIs, or MAOIs; stopping SNRIs or SSRIs may be helpful since they can cause sexual dysfunction.
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