Dr Laura T SafarLaura T. Safar, MD
Patients with multiple sclerosis (MS) are challenging to treat, even with the multitude of advances that have been made in the last decade. One of those reasons is the high presence of comorbidity in these patients, and particularly, addressing mental health concerns. 

As Laura T. Safar, MD, assistant professor, psychiatry, Harvard Medical School, and director, MS neuropsychiatry, Brigham and Women’s Hospital, notes, this comorbidity can lead to additional understanding of the pharmacologic interactions between the different treatments that patients may be administered. In a discussion with NeurologyLive®, Safar offered insight into this process, and noted the need for a personalized approach for such a complex disease.

Utilizing collaborative care models as well as additional time and effort, she said, can help avert the oversimplification of prescribing patients a drug that may, in turn, worsen their condition.

NeurologyLive®: Why is it so important for clinicians to be aware of psychopharmacology in patients with multiple sclerosis?

Laura T. Safar, MD: The reason why that is important is that the prevalence of psychiatric disorders is very high in MS. For any given psychiatric disorder, the prevalence is 2 to 3 times higher in patients with MS than in the general population, and while we do not think of psychopharmacological agents as the only answer to treat psychiatric symptoms, it's certainly 1 tool that we have. It can be very helpful and improve patients' quality of life, coping with MS, adherence to disease-modifying therapies, etc.

One of the many interesting points is that there are very, very few trials of antidepressants and all the different types of agents, specifically for patients with MS. When we are sitting with a patient with bipolar disorder, for instance, and MS, we tend to select the agents primarily using the same thinking algorithm that we would use for general psychiatric patients. However, for each one of the groups of different agents, there are certain pearls, or take-home messages, that are specific to MS that clinicians should be aware of.

Do you have a take-home message for clinicians regarding antidepressants?

First and foremost, the most important take-home message is not to oversimplify. Not to think that an individual with MS has depression that this just a vanilla major depressive disorder and you can just write a prescription for an SSRI. It's to take the time—it takes more time and effort for the clinician and other team members—to evaluate that there is sadness, and moving from there, is there a major depressive episode, and from there, what are the factors involved causing the depression, how much is the impact of pain from MS, is there a comorbid sleep disorder which will affect the depressive symptoms, did the depression start after the start  of disease-modifying therapy or steroids or is there possibly an impact from medications contributing to the depression? That's number 1, to do a thorough assessment.

Once you decide that "OK, yes, this person has major depression and would benefit from an antidepressant," even the most benign psychotropics, in a patient with a neurological illness, their brain is more sensitive. You want to be cautious when you prescribe, and you want to start, generally, with lower doses and go up slower. You also want to consider the comorbidities—there is a high comorbidity of [periodic limb movements of sleep] as well as restless legs syndrome in MS. SSRIs, which are the most commonly prescribed antidepressants, can worsen restless legs syndrome, so you want to pay attention to that in patients with MS.

Another lesser-known adverse effect of antidepressants is that, in the long-term, if they are used for many years, they can contribute to bone fragility. In patients with MS who have a risk for falls, that becomes more important than it would in the general population.

What should clinicians treating MS know about prescribing antipsychotics in this population? 

The antipsychotics, classically, are divided into the conventional and the newer generation. Nowadays, clinicians are more likely to prescribe newer, second-generation antipsychotics because generally, they are more benign in terms of adverse effects and they are equally effective to the older agents. A specific point for MS includes that the agents that have higher potency in antagonism of the dopaminergic 2 receptor are more likely to cause extrapyramidal side effects like parkinsonism, problems with gait and movement, tremors, etc. In a patient with MS who already has gait problems, motor problems, you will typically want to avoid—risperidone is one example—but in general those agents with a higher degree of D2 antagonism.

Another thing that applies specifically to patients with MS is that some agents are more sedating than others. An example is quetiapine, which is very helpful in low doses for sleep and for agitation, but if you have a patient who is already psycho-motorly retarded with severe fatigue, you would likely avoid it in that patient and prefer something that is more activating.

Transcript edited for clarity.