Several factors should be considered when choosing a medication and dosing schedule for this depressed adult male who reports being "very sensitive" to medication and expresses particular concern about being either sedated or "revved up" from an antidepressant.
A 37-year-old male commercial realtor with a 2-month history of feelings of sadness and loss of interest in recreational activities reports difficulty focusing his attention at work, anorexia with weight loss, and early morning awakening. He also finds it increasingly difficult to drag himself out of bed in the morning to go to work. After evaluating the patient, you make a diagnosis of major depression. He reports being “very sensitive” to medication and expresses particular concern about being either sedated or “revved up” from an antidepressant.
What factors should be considered when choosing an antidepressant and its dosing schedule?
Because of the length of time the patient has been suffering from depression, his functional impairment both at work and home, and his neurovegetative symptoms, antidepressant treatment would be recommended. Though all antidepressants are thought to be equally effective regardless of symptoms, a patient may be more likely to tolerate one medication over another based upon symptoms and likely medication side effects. For example, a patient with prominent anxiety symptoms may be less likely to be able to tolerate a more stimulating antidepressant like bupropion, even though the drug would be just as likely as another antidepressant to decrease anxiety symptoms if the patient completed his or her course of treatment.
In this instance, the patient is concerned about side effects and reports difficulty with medication in the past, so a serotonin selective reuptake inhibitor (SSRI) is most likely to be well tolerated. Since the patient has difficulty with appetite and weight loss, medications such as fluoxetine that have more prominent gastrointestinal (GI) side effects should probably be avoided. Additionally, a drug that is not stimulating and might even be slightly sedating would address this patient’s concerns about daytime side effects if it were administered at bedtime. A safe choice would be citalopram.
You opt to start the patient on citalopram. How would you titrate the dosage in order to achieve the desired response?
As the patient is very concerned about side effects, it is appropriate to start at a low dose and increase slowly as tolerated. The dosing regimen for a patient who reports being “very sensitive” to drug side effects is similar to that employed in a geriatric patient, namely “start low and go slow.”
An initial citalopram dose of 10 mg at bedtime with a dosage increase to 20 mg after 4-5 days is appropriate. Though response to citalopram usually does not occur before 4-5 weeks, some symptomatic improvement is commonly seen within 2-3 weeks. If there has been no symptomatic improvement by that time, then a dosage increase in 10 mg increments to as high as 40 mg is indicated.
The patient’s dose is progressively increased to 40 mg daily. He has been on that dose for a month, yet reports minimal improvement in his symptoms. What are your options?
Most patients fail to experience full remission of their symptoms from the first selected medication. If the patient has a partial response, it is generally advisable to build upon it by increasing the dose or adding a second antidepressant. When the first drug fails to produce any significant improvement in symptoms, a medication switch is advised.
A switch in medication is indicated in this patient due to the lack of significant improvement in his symptoms and the potential risk of QT prolongation and arrhythmia from the daily use of citalopram dosages exceeding 40 mg, as reported by the US Food and Drug Administration (FDA).
You decide to discontinue citalopram and switch the patient to another antidepressant. What antidepressant would you favor? Would his symptoms improve more significantly if he were switched to an antidepressant that is not an SSRI?
If a patient has failed to respond to an SSRI antidepressant, common wisdom tells us that a switch “out of class” to a serotonin norepinephrine reuptake inhibitor (SNRI), for example, is more likely to be effective. However, there is very little evidence that converting to a different class of medication makes any significant impact on the second medication’s effectiveness. Therefore, a second SSRI that would be well tolerated is a better choice.
In light of the favorable side effect profile of SSRIs, as well as the fact that they are among the most commonly prescribed medications, what patient characteristics or clinical circumstances would cause you to recommend a different antidepressant class?
Because all antidepressants are equally effective, an SSRI is usually a suitable first choice, as the whole class is safe and well tolerated. However, there are certain specific circumstances in which another class of medications may be preferentially indicated.
A depressed patient with chronic pain might prefer dual reuptake inhibitors — which include SNRIs, tricyclic antidepressants, and mirtazapine — because they treat depression symptoms just as effectively as SSRIs, but they more effectively treat pain symptoms. For patients who have a history of sexual dysfunction with SSRIs and are unwilling to consider another drug in its class, both bupropion and mirtazepine should be considered because they have a very low risk of producing that side effect. Options for patients who have failed to benefit from commonly prescribed medications would include monoamine oxidase inhibitors (MAOIs). However, most MAIOs require special dietary precautions, so they are not generally used.
You decide to switch the patient to sertraline. How would you conduct the transfer from citalopram?
It is important to be cautious when administering 2 SSRIs at the same time because of the risk of “serotonin syndrome,” which is marked by agitation, flushing, palpitations, and alterations in mental status. It is not necessary to stop one drug before starting the next, but it is a good idea to reduce the dose of the first drug. Tapering citalopram to 20 mg over the course of a week before starting sertraline 50 mg is indicated, and then tapering the patient off citalopram while increasing the sertraline dose to 100 mg as tolerated is usually an effective strategy.
The patient reports improvement on sertraline 100 mg without any significant side effects. He has become much more sociable and his mood has improved, but he continues to experience difficulty at work, anxiety, insomnia, and anorexia. How would you manage him at this point?
The goal of treatment for major depressive disorder (MDD) is the complete elimination of symptoms. Residual symptoms lead to continued disability at work and home, and they increase the risk of relapse of all depression symptoms. As this patient is not experiencing any dose-limiting side effects and has not yet received the maximum recommended dose of sertraline, his dosage should be increased to 150 mg.
You increase the dose to 150 mg for 3 more weeks, and while the patient improves somewhat, he still is not fully recovered and exhibits residual anxiety. What would you advise at this point?
This patient has demonstrated a great response to sertraline, albeit a partial one, so combination treatment is now called for to eliminate residual symptoms of depression. Because the core symptoms of depression have been resolved, the use of a second antidepressant may not be the most effective treatment at this point. One strategy is to specifically target the anxiety by adding buspirone, which is effective in many patients with anxiety secondary to depression and does not carry the risk of drug dependency that can be seen with benzodiazepines.
You add buspirone to sertraline, and 6 weeks later, the patient reports that he nearly feels back to normal. However, insomnia continues to be a problem. What options do you have for managing insomnia?
Patients can have difficulty sleeping through the night, either as a residual symptom of depression or as a side effect of an SSRI. In either case, a low dose of trazodone 50-100 mg can be a safe and effective strategy to relieve insomnia symptoms on an as-needed basis.
The patient’s insomnia improves and he begins dating again, though he soon discovers erectile dysfunction with reduced libido. What options are available for managing this side effect?
Though decreased libido and erectile dysfunction are common SSRI side effects, they are dose-dependent for some patients. Therefore, slightly reducing the dose of the SSRI once a patient has recovered from depression and been stable for several months may relieve the symptoms of sexual dysfunction while maintaining antidepressant effectiveness.
If this does not work, either from persistent sexual dysfunction or the return of depressive symptoms, then medication for the treatment of erectile dysfunction can sometimes adequately address issues of sexual performance. However, it is more challenging to adequately address the problem if it is primarily a reduction in libido. The most common approach is to add bupropion 75-150 mg daily, which resolves the issue in a significant number of patients.
The patient returns 8 months into his therapy and reports that everything is going “great.” He wants to know how long he needs to stay on antidepressant therapy. What do you tell him?
Current guidelines call for continuing treatment at a full dose for an additional 4-9 months from the time a patient has experienced complete remission of symptoms. How long treatment is continued depends upon the patient’s history.
The lifetime risk of depression recurrence is 50% after an initial episode, 75% after 2 episodes, and 90% after 3 episodes. Whenever treatment is discontinued, the risk of recurrence increases. How soon treatment is stopped, if at all, depends not only upon the number of prior episodes, but also the severity of the immediate past episode. Even if the most recent episode was the first, it may warrant consideration of a longer or perhaps indefinite continuation period if it was particularly severe and prolonged.
Other factors that can help determine how long a patient is maintained on continuation treatment include the severity of side effects and whether the patient wishes to have children in the near future if she is a woman of childbearing age. Ultimately, the decision on how long to continue treatment is a complex cost-benefit analysis that follows a consultation between the patient and treating physician.
About the Author
Andrew Leuchter, MD, is Professor of Psychiatry and Behavioral Sciences at the David Geffen School of Medicine at UCLA. All questions were posed by Family Practice Recertification Editor-in-Chief Martin Quan, MD.