Laura T. Safar, MD, on Psychopharmacology and Multiple Sclerosis

Mood disorders are common among patients with multiple sclerosis (MS), and psychotropics are one option for treating this patient population.

At the Consortium of Multiple Sclerosis Centers Annual Meeting 2019, Laura T. Safar, MD, and her colleague Jane Erb, MD, reviewed and updated clinicians on the use of psychotropics among patients with MS.1

Neurology Consultant caught up with Dr Safar after her presentation. Here are her answers to our burning questions.

Laura T. Safar, MD, is an assistant professor of psychiatry at Harvard Medical School, associate neuropsychiatrist at the Brain/Mind Medicine Center at Brigham and Women's Hospital, and the director of BWH Multiple Sclerosis Neuropsychiatry at Brigham and Women's Hospital in Boston, Massachusetts.

NEUROLOGY CONSULTANT: Can you give us an overview of your session?

Laura T. Safar: Psychiatric disorders are highly prevalent in patients with MS, much more so than in the general population. For instance, the lifetime prevalence of major depression in individuals with MS has been estimated, in different studies, to range from 25% to 50%.

The lifetime prevalence of other psychiatric disorders in individuals with MS are as follows:

  • Bipolar disorder: about 6%
  • Pseudobulbar affect: 10%
  • Anxiety disorders: about 25%
  • Cognitive disorders: more than 40% 


The presence of psychiatric disorders may have a substantially negative impact on the individual’s quality of life, adherence to MS treatment, functional status, and MS treatment outcome. For all these reasons, it is very important to screen for psychiatric disorders, and diagnose and treat the patient properly. Psychopharmacological agents are one option for treating these disorders. 

NEURO CON: Which psychotropics are appropriate for which MS patient populations?

LTS: All psychotropics are potentially appropriate for use in patients with MS. The selection of agents must be done case by case according to the individual patient’s psychiatric symptoms, the known therapeutic and side effect profiles of each agent, and other factors such as interactions with other medications.

Antidepressants, antianxiety agents, mood stabilizers, antipsychotics, and cognitive enhancers all have a role in the treatment of psychiatric disorders in individuals with MS. There are specific considerations to take into account when using psychotropics in MS, though. For instance, among the antidepressants, serotonin reuptake inhibitors (SSRIs), serotonin-norepinephrine reuptake inhibitors (SNRIs), or bupropion can be considered first-line treatments in the general population. For patients with combined depression and anxiety, an SSRI or an SNRI would be preferred.

Examples of commonly used SSRIs are sertraline, citalopram, escitalopram, and fluoxetine. Examples of SNRIs are duloxetine and venlafaxine. For patients with depression and prominent physical and cognitive fatigue—a common MS symptom—an SNRI or bupropion may be preferred over an SSRI, since these medications’ noradrenergic activity may help increase patients’ energy level and cognitive focus. In addition, SNRIs can help reduce certain types of pain, including neuropathic pain.

NEURO CON: Is it appropriate for neurologists to prescribe psychotropics to their patients with MS? At what point in the treatment course should a psychiatrist be consulted?

LTS: In my experience working with neurology colleagues, many neurologists who treat patients with MS are comfortable prescribing psychotropics for patients with less-complex psychiatric presentation. For instance, they feel comfortable diagnosing major depression and prescribing an SSRI. I do think this is appropriate, for several reasons.

For instance, many patients with MS have a trusting, longitudinal therapeutic relationship with their MS neurologist. They may feel comfortable disclosing psychiatric symptoms in this setting. This puts the neurologists in a good position to identify the presence of depression and to offer treatment. In addition, we know that, at least to some extent, the psychiatric symptoms may be part of the MS manifestations—in other words, psychiatric symptoms can be a direct, biological consequence of the illness. Neurologists can provide integrated treatment, instead of referring the patient to a mental health provider and increasing fragmentation of care.

However, for patients with more complex presentations, the best response is to work in an integrated manner with a psychiatrist and other mental health professionals. Those complex presentations may include symptoms of bipolar disorder; severe, treatment-resistant depression; psychosis; or prominent cognitive impairment.

In addition to the complex cases, one could argue that psychiatrists should be consulted whenever the neurologist does not feel confident or comfortable making a therapeutic decision alone. This does not necessarily imply a referral to a face-to-face psychiatric consultation. A curbside consult can assist with simple questions, such as how to titrate the dose of a given antidepressant.

Lastly, while the focus of our course was psychopharmacology, the role of psychotherapy is fundamental to treat depression and anxiety, and to assist individuals with adaptive coping and to live well with MS. Reaching sooner rather than later and working as a team with a psychotherapist, integrated with the MS team, is invaluable.

NEURO CON: In terms of drug-drug interactions or adverse events, are some psychotropics better tolerated than others? What are your tips for managing these events for neurologists?

LTS: The whole list of drug-drug interactions and adverse events can be endless and exceeds the scope of this article. Some common and useful examples to take into account are:

  • Fingolimod can cause a prolongation of the QT interval. Some psychotropics, such as citalopram, escitalopram, amitriptyline, quetiapine, and ziprasidone, can also cause this adverse effect. It is preferred to avoid the combination of fingolimod and these agents.
  • Lithium can cause polyuria. In the case of a patient with MS and bladder dysfunction, this adverse effect can be particularly bothersome.
  • Some sedating medications, such as benzodiazepines and quetiapine, can worsen MS-related fatigue and cognitive dysfunction.
  • Antipsychotics, such as conventional antipsychotics or risperidone, with a high degree of Parkinsonian adverse effects, can further compromise the gait of a patient with MS and increase the risk for falls. 


NEURO CON: What is your key take-home message for neurologists?

LTS: Remember to screen for the most prevalent psychiatric disorders in individuals with MS: depression, anxiety, and cognitive difficulties. Remember to screen for suicidal thoughts, as suicidal ideation, intent, and attempts are also more frequent in patients with MS than in the general population. Educate yourself and seek training on the most common psychiatric presentations and differential diagnoses, and become comfortable with a small toolset of psychotropic agents you can manage. As possible, work with an interdisciplinary team, including a psychotherapist/case manager, a psychiatrist, and other professionals. Be aware of different models of integrated care. Sometimes a patient may need a referral to a psychiatrist, but given the shortage of psychiatrists and other mental health professionals, other care models, such as having a psychiatrist as a consultant in your practice, can be helpful.


Safar L. Use of psychotropics in MS: antidepressants, antianxiety agents, mood stabilizers, antipsychotics, cognitive enhancers, and cannabis. Course presented at: Consortium of Multiple Sclerosis Centers Annual Meeting 2019; May 28-June 1, 2019; Seattle, WA. Accessed June 17, 2019.