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The Deep and Multidimensional Connection Between Multiple Sclerosis and Depression

— Both depression and suicide rates are high in MS patients, but there are effective treatments

Ƶ MedicalToday
Illustration of ways of managing depression over multiple sclerosis
Key Points

"Medical Journeys" is a set of clinical resources reviewed by doctors, meant for physicians and other healthcare professionals as well as the patients they serve. Each episode of this journey through a disease state contains both a physician guide and a downloadable/printable patient resource. "Medical Journeys" chart a path each step of the way for physicians and patients and provide continual resources and support, as the caregiver team navigates the course of a disease.

When it comes to any kind of chronic condition, patients are all too likely to develop depression as they navigate the associated stresses and challenges. But with the chronic demyelinating disorder multiple sclerosis (MS), there appears to be even deeper connections with depression, noted Scott Patten, MD, PhD, the Cuthbertson and Fischer Chair in Pediatric Mental Health at the University of Calgary in Canada. These include biological mechanisms like hippocampal microglial activation, lesion burden, and regional atrophy.

The relationship between the two conditions is complex, he told Ƶ. "There was a period in psychiatry when people tried to differentiate the psychological from the biological aspects of depression in MS, asking, for example: Is it the burden of lesions? Is it the location of lesions? The modern perspective, however, is that we should just accept that depression is a biological, psychological, and social entity. You'll get better outcomes by addressing that multidimensional nature with your patients."

Diagnosing Depression

It may be worth occasionally revisiting the DSM-V criteria for Major Depressive Disorder. A was released in 2022. A requires at least five of these nine criteria:

  • Depressed mood
  • Loss of interest or pleasure in almost all activities
  • Significant (more than 5% in a month) unintentional weight loss/gain or decrease/increase in appetite
  • Sleep disturbance (insomnia or hypersomnia)
  • Psychomotor changes (agitation or retardation) severe enough to be observable by others
  • Tiredness, fatigue, or low energy, or decreased efficiency with which routine tasks are completed
  • A sense of worthlessness or excessive, inappropriate, or delusional guilt (not merely self-reproach or guilt about being sick)
  • Impaired ability to think, concentrate, or make decisions -- indicated by subjective report or observation by others
  • Recurrent thoughts of death (not just fear of dying), suicidal ideation, or suicide attempts.

Symptoms must have been present for at least 2 weeks in a row and persist for most of every day. Additionally, the DSM-V requires that symptoms "cause clinically significant distress or impairment in social, occupational, or other important areas of functioning."

Regarding treatment for comorbid MS and depression, a noted that the path forward in treating depression is not always clear. "There is currently no gold-standard, single treatment for depression in MS," the authors wrote. "Combinatory treatments may be efficacious for treating [major depressive disorder] and managing its consequences in MS."

Cognitive behavioral therapy (CBT) and antidepressants are the two most commonly used therapies in people who have both MS and depression.

CBT and MS

CBT is intended to be a short-term therapeutic course to help patients recognize and redirect negative thought patterns during therapy and in the future. The therapist often helps the patient achieve this goal by assigning written homework to aid in self-reflection.

Patten and colleagues explained in a that while there are robust data indicating the effectiveness of CBT in MS, there are also challenges specific to MS. "Delivery of cognitive behavioral therapy needs to address visual problems, cognitive deficits, and dysgraphia in its use of homework assignments," the team wrote, noting that all these issues are common symptoms of MS.

The "behavioral activation" aspect of CBT can be challenging for people with MS. "Many general CBT therapists will offer suggestions like go for a brisk walk each morning or sign up for a sport or gym membership, but patients have to do it at the right pace or risk making themselves sick," Patten cautioned. "Patients need to find ways to be more active that fit with their illness, and seeing a CBT therapist who understands MS can be extremely positive."

Antidepressants and MS

Just as a degree of treatment customization can make all the difference in CBT for people with MS, the same is true for antidepressants. But which antidepressants should prescribers turn to for patients with MS?

In general, Patten suggests zeroing in on one or two antidepressants to use first. "There are about 30 antidepressants out there, all of which probably have the same efficacy that they would have outside of the MS population," he said. "There's no way a neurologist should be expected to be familiar with more than one or two. Pick a small number of antidepressants and learn to use them with confidence."

Of course, the specific symptoms of the patient sitting in front of you should help guide your prescribing choices, Patten continued. This area of scientific literature, however, may not be of much help to prescribers, he added. "One trial was done with nortriptyline and another focused on paroxetine. These are not medications that are viewed as the first choice by most people nowadays."

Patten offered the following to consider:

  • Sedating versus non-sedating medications: "Anything sedating is going to aggravate fatigue and put patients at risk of falls because it may negatively affect balance and coordination. So, there is a general preference for non-sedating antidepressants," he said.
  • Autonomic symptoms: "Many patients with MS have issues with GI upsets and sexual dysfunction arising from the illness, so be sure to consider whether your patient has these issues when choosing an antidepressant to avoid aggravating autonomic symptoms."
  • Neurogenic pain: "If you're already using low doses of amitriptyline for neurogenic pain, consider that increasing the dose slightly may get the patient into the therapeutic zone for depression, too."
  • Anticholinergic medications: "Some tricyclic antidepressants have anticholinergic side effects that aren't related to the condition they treat. They include confusion and memory problems, as well as bladder function issues and constipation."

Preventing Suicide

Suicide risk is a crucial element of managing patients with double MS/depression comorbidities. An older but well-regarded found that the risk of suicide was approximately doubled in people with MS.

"For about 20 years, we've accepted that the suicide risks in MS patients are probably double the overall population rate, especially during the first year after diagnosis," Patten said. "More recent studies have shown us a weaker association of suicide, which probably reflects better management of both MS and depression, but there is unquestionably a greater suicide risk."

Patten said that with everything needing to be covered in a clinic visit, busy non-psychiatrists may relegate the subject to an afterthought. Patten recommends using a different tactic: addressing any concerns directly with patients. "Many clinicians are not comfortable with the topic of suicide, so they avoid it," he noted. "That is not a good idea in a population that's already high risk. Clinicians must be comfortable talking about suicide with patients and helping them formulate a safety plan if needed."

Clinicians may find that addressing less tangible issues like depression or anxiety can feel less urgent than, say, focusing on a vision deficit or mobility issue. However, Patten said he has found that the payoff of tending to patients' mental health can be substantial.

"This group of patients must constantly adapt and accommodate the neurological side of the illness to get on with their lives. That requires some optimism and energy, and when people get depressed, those things can be in short supply," Patten said. "But when you look at what factors determine quality of life in MS, depression is way up there. It's worth our focus as clinicians hoping to achieve the best possible outcomes for our patients."

Read previous installments in this series:

Part 1: Early Diagnosis Can Mean Better Outcomes in Multiple Sclerosis

Part 2: How Does Multiple Sclerosis Start?