My Testimony to the Standing Committee on Veterans Affairs on Mefloquine (April 29, 2019)

Mesdames et messieurs, thank you for giving me this opportunity today.  It’s quite humbling, as I do not consider myself an expert in quinism.  Instead, I’m an expert in operational stress injuries, or OSIs: those diagnoses that arise from the stress of military training and operations, including PTSD, depression, adjustment reactions, and any of the myriad other problems that arise as a result of being thrust into extremely demanding situations.

I’m very pleased that the committee will be hearing from the real experts on quinism.  In particular, I have learned much from Dr. Remington Nevin, who has studied quinism extensively, and will be able to teach you much more than I can about the neurological damage that it causes.

I’m here today primarily because I have listened to Veterans.  Through doing so, I have learned about the challenges associated with mefloquine, including the difficulty that diagnosing it can represent.

I have worked with Veterans for about 15 years now, and as part of my work, I have completed many psychological disability assessments.  For most of these, the issues associated with quinism have not been on my radar.  It’s simply not something there’s much awareness of in my field.

To diagnose an operational stress injury, I begin with a clinical interview.  I need to understand the Veteran’s presenting symptoms, and I gather a history, so that I can understand how they were functioning before and after the exposure to the military.  

I look at the operational history of the Veteran, including what tours they went on, and what traumatic events occurred.  We look at physical injuries, including exposure to blasts, as well as any other physical issues which might arise from the rigors of training and deployment.

I review what documentation I might have available (which is often pretty scant), and I administer psychological tests.  From these, I’m able to identify the Veteran’s symptoms, and in combination with the history, I can draw conclusions about the diagnosis, and its probable link to military service.  

I’d like to take a moment to review the diagnostic criteria for PTSD. You may already be reasonably familiar with these, but please bear with me, as I think it’s worth reviewing them in this context.  

The diagnosis of PTSD is rather unique among psychiatric diagnoses.  That’s because diagnosis begins not with the symptoms presented by the patient, but with an examination of the event.  

Criterion A is directly experiencing, or witnessing, actual or threatened death, serious injury, or violence.  
In the course of their careers, many, if not most, Veterans will experience an event which meets Criterion A.  However, they don’t all end up with PTSD.  They must experience symptoms which arise following the event:

Criterion B requires one intrusion symptom:
• Intrusive memories of the event
• Recurring dreams in which the content or mood of the dream reflects the trauma
• Dissociative reactions, such as flashbacks in which the person feels or acts as if it’s happening 
• Intense or prolonged psychological distress at exposure to reminders of the event
• Physiological reactions to reminders of the event

Criterion C requires one avoidance symptom:
• Efforts to avoid distressing memories, thoughts, or feelings associated with the event
• Efforts to avoid external reminders of the event, such as people, places, conversations, activities, or situations

Criterion D references two symptoms of negative alteration in cognition or mood:
• Inability to remember some aspect of the event
• Exaggerated negative beliefs about oneself, others, or the world: “I’m broken,” “No one can be trusted” 
• Distorted beliefs about the cause of the event, leading to blame of self or others
• Persistent negative emotional state (fear, anger, guilt, shame)
• Withdrawal from activities
• Feeling detached or estranged from others
• Inability to experience positive emotions

Criterion E references two symptoms of alteration in arousal and reactivity
• Irritability or angry outbursts
• Reckless or self-destructive behaviour
• Hypervigilance
• Exaggerated startle response
• Problems with concentration
• Sleep disturbance

Criteria B through E represent the symptoms of PTSD, and in each case, there should be evidence that the symptom began or worsened following the trauma.  In these symptoms, you’ll find the echoes of other OSIs, including depression, or anxiety disorders.  Substance abuse can be used to self-medicate and mask many of these symptoms; those who have strong reactions to events that don’t meet Criterion A might be diagnosed as having an adjustment disorder.  All of these are common OSIs. 

For our purposes, there’s one more important criterion for PTSD: Criterion H says these symptoms must not be attributable to the physiological effects of a substance—such as mefloquine.

That final criterion is pretty close to universal in DSM-5, as it’s found in the diagnostic criteria for most disorders.  It’s so common, it’s actually easily overlooked; when you’re dealing with psychological trauma, it’s rare to see someone in clinical practice whose symptoms can be attributable solely to the effects of a substance.  In fact, before I’d heard of mefloquine, I was not aware of any substance which could mimic PTSD.  And this substance was often prescribed in proximity to a traumatic event.

When we look at the symptoms of quinism, we’re going to see that they mimic many of the symptoms of PTSD and other OSIs.

According to the work of Dr Nevin, the adverse effects of mefloquine can include the following psychiatric symptoms:
• Anxiety
• Depression
• Panic attacks
• Severe mood swings
• Agitation
• Aggression
• Restlessness
• Mania (racing thoughts, irritability, paranoia, excessive goal-driven behaviour, euphoria)
• Psychosis
    o Paranoia
    o Delusions
    o Hallucinations
• Dissociative symptoms such as derealization and depersonalization
• Sleep disturbance, including terrifying, intense nightmares, or sleep paralysis (an experience like being awake in a body that will not move, often with a terrifying hallucination)

With varying degrees of frequency, all of these symptoms can, and do, present as sequelae to exposure to psychological trauma.

I’m thinking of two Veterans I’ve worked with.  Both meet Criterion A for PTSD. Both present with an unusual feature, which I rarely see in OSIs: Hallucinations. Only one was exposed to mefloquine, and he experienced the full prodromal reaction: nights of severe terror, punctuated with what seemed to be auditory hallucinations of animals screaming in the forest surrounding him.  Today, he suffers from tinnitus and a persistent auditory hallucination, consisting of mumbling voices, along with other more typical symptoms such as irritability, anxiety, and mood disturbance.

It was years after his initial diagnosis of PTSD that the issue of mefloquine came up—and that was the first time I’d ever heard of the word.  I only heard about it because he brought it to my attention.

As we’ve seen, PTSD should not be diagnosed when the symptoms can be explained by the impact of a substance, such as mefloquine.  Does this mean that his diagnosis is not accurate?  Frankly, it’s possible. But I think the question may be more complex than a simple “yes or no” answer.

One of the challenges in clarifying the diagnostic conundrum is that Veterans may not always be able to accurately reconstruct the order in which events occurred, particularly vague events such as the emergence of a symptom.

Let’s consider a possible timeline:  A soldier is deployed overseas, on his first tour of duty; there are no prior exposures to traumas.  To prevent malaria, the soldier receives a course of mefloquine; he and his buddies joke about how rough their Friday nights are, after they’ve received the weekly dose of the drug, but they’re either not aware of the risks of continuing to take it, or they dutifully push through.  Almost immediately after treatment, the soldier is exposed to a war zone, with all the horrors that entails.

When the subsequent symptoms arise and persist, are they solely due to the mefloquine? Are they solely due to the exposure to trauma?  

Soldiers are not always the greatest historians. After years of pushing their emotions to the side, and ignoring discomfort, it can be difficult for them to remember precisely when a symptom arose. In the midst of a war zone, it’s only natural to be anxious, vigilant, and irritable.  Years may pass before the psychological injury is assessed. How are we to say whether the symptoms are due to quinism or trauma?

There are some symptoms, more neurological in nature, that might be helpful—things such as difficulty with balance, vision, vertigo, or tinnitus, which do not typically present solely as the result of PTSD.  Again, though, these have their own confounding variables—including the impact of blast injuries and concussions.

And of course, if the mefloquine was taken not on the first tour, but after the soldier has already been exposed to chronic trauma, then exposure to mefloquine may or may not account for subsequent symptoms.

The interaction between quinism and OSI may prove to be quite complex.  Consider, for example, research on how MDMA, or ecstasy, can help Veterans overcome traumatic memories—in a nutshell, a drug which induces feelings of warmth and compassion, when paired with a traumatic memory, helps to settle the anxiety provoked by that memory, with lasting effects.
Is it not likely that quinism does the opposite—a drug which provokes a chronic state of anxiety, when paired with a trauma, leads to a greater likelihood of PTSD?

In some tragic circumstances, there may be another source of trauma—actions taken while under the influence of the drug could lead to horrific moral injuries. I understand that soldiers in the Airborne Regiment in Somalia were given mefloquine. Imagine being such a soldier. You might find yourself asking how you came to violate your values and your duty by acting violently and illegally.  Though it may not meet Criterion A, perhaps the reaction to the drug is a kind of trauma in itself—is there anything more traumatic than having your very self, including your values and your sense of reality, stripped away?

Our understanding of quinism is in its infancy.  We have yet to grapple with its impact on the diagnosis, misdiagnosis, overlapping diagnosis, or exacerbation of Operational Stress Injuries, in part because too few of us are sufficiently aware of the need to screen for mefloquine exposure, and subsequent reactions to that exposure. 

In our ignorance, we’re also at risk of creating Sanctuary Traumas.  A Sanctuary Trauma occurs when someone expects to find help and support, but instead, experiences invalidation and rejection.  Research shows that the experience of such injustice can have a severe impact on recovery from physical and psychological injuries.  

Therefore, it’s imperative that the Veterans coming forward with stories of quinism have access to well informed case managers and clinicians; and that means we must disseminate what we know, and do the research necessary to learn more, so that we know best how to assess and treat this complex condition. 

Certainly, we need to start asking the questions, both as clinicians and researchers.  I am grateful that the Ministry is asking the questions that need to be asked.  I hope I’ve been of some help to you in that quest.  Thank you for your time. Merci. 

--Dr Jonathan Douglas