The subtle science of using medication to treat Posttraumatic Stress Disorder

Treating PTSD is a profound experience.

Helping someone battle their monsters is rewarding and difficult. But it also requires creativity in your approach and careful attention to your own countertransference. As I noted in a previous blog post, our own monsters can be stirred up along the way and so having your own therapy is important.

In the right environment there is hope. It provides a safe and containing space in which recovery can occur.

In this blog post I will focus on the pharmacological management of PTSD and draw upon the neuroscience to shed light on why certain medications are used.

So I want to put a disclaimer up front:

The contents of this article are purely for educational purposes and do not constitute medical advice. For advice on medication for the treatment of PTSD, please see your psychiatrist.

Psychotherapy is the key

Though there are differences, the guidelines broadly agree: psychotherapy is central to treatment. Everything else needs to support this.

The evidence supports therapies like trauma-focused CBT and Eye Movement Desensitization and Reprocessing therapy (EMDR). Developmental trauma will also benefit from Dialectical Behaviour Therapy (DBT), Schema Therapy, Cognitive Processing Therapy (CPT), Acceptance and Commitment Therapy (ACT), and psychodynamic psychotherapy.

This is just a list without explanation of what these are - because I really want to get to the subtle science of medication in the treatment of PTSD. The choice of therapy is an art itself needs to be tailored to the individual and draw from the therapist’s strengths. I find that I hover across these but emphasise psychodynamic approaches.

But I find that the best outcomes happen when psychotherapy is part of an orchestrated whole involving medication, social and environmental interventions, and complimentary therapies such as yoga and animal assisted therapy.

How this looks needs to be co-constructed with the patient. After all, the healing acts through them. It helps to have a deep understanding of the rationale behind treatment choices, especially early in treatment when the patient relies heavily on your support as a clinician.

Medication can be critical in the early phase of treatment but it serves the larger goal.

Medication fosters engagement

Therapy is hard work. And hard work is even harder when the limbic system is in overdrive from disrupted brain circuits.

So how does medication work in PTSD? From a neuroscientific perspective, there are essentially three components to it:

Medication that improves the control of the subjective experience of fear;
Medication that reduces the fight-flight response and intrusion symptoms; and
Medication that engages cognition and regulates emotion.

A rational approach to prescribing draws on this neuroscientific understanding to synergies between a multimodal approach and support psychotherapy.

This is where the guidelines fall short. The Australian guidelines for instance have a prescribing algorithm that is helpful but quite mechanistic. It reads a little like a prescribing algorithm for treating heart failure.

I like a recent paper by Dr Ani Gaspayan and colleagues. It hasn’t been cited very much but I find that it’s helpful to frame the clinical research beyond the guidelines. And it has easily accessible diagrams that link medication to symptoms.

Increasing control of the subjective experience of fear

I recently wrote a blog article on how the expience of fear involves cortical circuits. When the prefrontal cortex is overwhelmed by that fear, it struggles to control the limbic system.

I find that a good choice of antidepressent provides a solid base to the pharmacological management as it helps to reduce the overall level of anxiety by engaging the prefrontal cortesx. Why does this work? Because serotonin is a major modulator of the functioning of the prefrontal cortex.

From: Gasparyan A et al. Pharmacological strategies for post-traumatic stress disorder (PTSD): From animal to clinical studies. Neuropharmacology 2022; 218: e109211

There are a number of other antidepressants in addition to the SSRIs shown in the picture above. For instance, venlafaxine is a powerful antidepressant that also acts on noradrenaline in the brain to promote focus and energy, and therefore counter avoidance symptoms.

If a patient is already on an antidepressant, then I’m generally reluctant to change this, especially if they find it has some benefit. After all, changing antidepressants takes time and the goal is to reduce symptoms to help them engage with the therapy within a safe and containing environment.

Cooling down the fight-flight response

Arguably, the most distressing symptoms of PTSD are the hypervigillance and the nightmares and flashbacks. These are exhausting. The impact on sleep in turn impacts the functioning of the cerebral cortex, which is ostensibly the target of therapy. This is where antihypertensive medication help.

The cerebral cortex has receptors that respond to adrenaline. They play a role in arousal, mood, and memory. Blocking them reduces hyperarousal in PTSD and interestingly nightmares and flashbacks also diminish, particularly the alpha-1 receptors. Stimulating alpha-2 receptors with clonidine and guanfacine also produces a similar effect and opens up a broader range of options.

Engaging cognition and regulating emotion

Dopamine is a critical neurotransmitter for focusing the mind. Stimulants for ADHD exploit this. Older antipsychotics tend to block dopamine across the brain, which in turn impacts cognition while they’re treating psychotic symptoms. The newer antipsychotics take advantage of serotonin pathways in the frontal lobes to increase the amount of dopamine, and thereby protect against the cognitive side effects of antipsychotics.

The limbic system - the emotional part of the brain - is also regulated by the prefrontal cortex via dopamine pathways that are inhibited by antipsychotics. Whilst this is the target of hallucinations and delusions in psychosis, it also enhances the control of the limbic system by the prefrontal cortex.

The choice of an antipsychotic in PTSD depends on a number of factors, but I find that only relatively low doses are needed compared with a psychotic illness, and so their use in PTSD is well tolerated. Interestingly, Gasparyan and colleages found that quetiapine isn’t well supported by the evidence even though this is the only antipsychotic recommended in the Australian guidelines.

Is this polypharmacy?

It is important to keep in mind that psychotherapy is the key. It’s like the Sam Kerr of the Matildas, but she can’t kick goals without the support of a strong midfield.

A combination of these medications must be managed by a specialist. There are multiple interactions and side effects that need to be carefully managed. There are a number of other pharmacological options available as well and there are also novel treatments. But the medication that I’ve discussed here are the foundational classes of medications.

No one wants to be overly sedated. A sedated patient will struggle with therapy.

When chosen rationally using a neuroscientific basis, prescribing multiple medications are not polypharmacy. Their choice is purposive with a goal in mind, namely to engage with therapy.

I’d like to reinforce that this article is purely educational. I hope that you enjoyed it!