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How you take medication for your mental health matters

This is the fourth and final article in a series inspired by EU-PEARL (EUropean-Patient-cEntric clinicAl tRial pLatforms). The EU-PEARL project aims to shape the future of clinical trials, creating a framework for platform trials.


Psychiatric medications are a critical part of the treatment plan for many living with mental health disorders. In fact, data on prescribing trends across GP practices in England show that, between 2020 to 2021, a total of 79.4 million antidepressant drug items were prescribed to 7.87 million identified patients.


For many, the necessity of these antidepressants is undeniable, and with such high numbers of people receiving them, one important consideration for researchers, patients, and doctors alike is: how exactly are these medications being administered to patients?


The route of administration can have a significant effect on how well a given drug treats symptoms, as well as affecting its safety, comfort, and convenience for the patient, each route coming with its own benefits and downsides. This article will explore the various routes of administration for psychiatric medications and the research that has been conducted on their acceptability in patient populations.

 

Alongside my role for Inspire the Mind, I’m also a research assistant at the SPI Lab at King’s College London and, although the project launched back in 2018, I began my work within EU-PEARL mid-last year. As you may remember from this introductory article, the EU-PEARL project’s mission is to ultimately create a novel, adaptive, and efficacious clinical trial platform via collaboration between research centres, non-profit organisations, hospitals, pharmaceutical companies, and the very patients that the trialled medications may one day help treat.

Thanks to the use of a ‘master protocol’, the introduction of the ‘platform trial’ paves the way to changing the way drug research and development takes place, allowing multiple potential drugs to be tested simultaneously and flexibly (i.e., if one drug is deemed unsuccessful, it can easily be removed from and replaced in the trial).

Expectedly, platform trials are also a great way to trial established and already approved medications, only this time for different purposes (e.g., an antibiotic or ketamine to treat inflammation and major depressive disorder) and via different routes of administration (e.g., an injection instead of a tablet).

What is ‘the route of administration’?

When it comes to treating psychiatric conditions, there are several ways we can approach them. While medications and psychotherapy are commonly used, understanding which route of administration — the way in which a treatment is given — is best suited for a patient is key and as such, requires careful consideration.

The delivery of the chosen psychotherapeutic care — whether it be as an oral tablet, intravenous (IV) injection, inhaler, nasal spray, or any other form — can impact a patient’s level of success. A patient’s success with an intervention refers to how well the invention (e.g., a medication) addresses the condition; for example, for a patient with depression, “success” would be measured by how well a chosen antidepressant reduces the depressive symptoms the individual otherwise experiences.

Though a range of other factors also play a role in how helpful a medication will be for a patient, such as when and how regularly it’s taken, whether it’s taken with another medication, or whether the patient has any other illness or any other mental health condition, for the purposes of this article, I will be focussing on the influence of the route of administration.

Orally administered medications

The most commonly used antidepressants globally all come in orally administered (any medication taken through the mouth) forms, including tablets, capsules, liquids, and oral drops.

Ease of administration is a big part of the reason oral medications are so widely produced and used; being able to carry a pill bottle around with you in your bag, taking your medication in the comfort of your own home, and not needing to speak to a healthcare professional before every dose are conveniences that we all certainly can appreciate.

Likewise, with relatively low manufacturing costs, less time spent in hospitals, clinics, or at the GP with healthcare staff, and absence of specialist equipment to administer your next dose, oral medications are generally far less expensive overall than, for example, IV infusions and inhalers.

However, although the convenience of taking tablets allows us to adapt our treatments to our own lives, this independence means that responsibility for administration lies (almost) solely with us. If a dose is missed, taken with the wrong food, not enough food, or with alcohol or recreational drugs, that’s on the patient, rather than the professional administering the dose directly within a controlled environment.

Moreover, some people simply cannot tolerate oral medications for a range of reasons, whether it be due to their taste, inability to swallow pills in general, past bad experiences, or possible side effects such as nausea or vomiting.

Also, compared to medications administered directly to the bloodstream or other target area, orally administered drugs can be slow in terms of absorption into the bloodstream due to digestion-related delays. This means that effects may not be felt as quickly as via other routes of administration after taking a dose and could be diminished when taken with food or other substances such as alcohol or recreational drugs.

Is this delay such a huge deal though, in the context of antidepressants? Potentially.

Those with experience or knowledge about how antidepressants work will know that, with most antidepressants, though time frames vary slightly depending on the type taken (i.e., SSRIs, SNRIs, TCAs, or MAOIs), typically, users only start to feel improvement to their symptoms after the first couple of weeks of consistent use, which can be understandably frustrating to some.

So, what options do patients have, and are there other routes of administration for these antidepressants that could improve this delay?

Alternatives to oral administration

Intravenous (IV) infusion therapy involves administering drugs through a needle directly into a vein resulting in fast absorption, though requiring hospitalisation until the procedure is finished. For many of us, this technique is probably most associated with cancer-treating chemotherapy sessions, but it’s certainly not limited to it. The need for specialist staff, equipment, and facilities is associated with increased costs not usually seen with orally administered medications.

The use of IV administration of antidepressant medication has long been an area of great clinical interest, with the primary rationale being the faster onset of action (i.e., how quickly the drug starts working in the body) compared to orally administered drugs. However, research suggests that this is only really the case depending on the drug.

For example, ketamine has demonstrated great potential as an antidepressant, as discussed by Dr Naghmeh Nikkheslat in an article for Inspire the Mind. Research investigating the impact of the route of administration, comparing oral ketamine to IV ketamine, found that despite the typical advantages of oral administration (i.e., more convenient, and accessible), it also comes with greater risk of abuse by users due to that removal of a controlled environment.

Though an oral form of ketamine for depression would be much more convenient for patients, this benefit doesn’t outweigh the fast action, high effectiveness, and high bioavailability (how much of the drug actually enters your bloodstream) of IV ketamine. Currently though, research on the practical real-world use of an antidepressant like oral ketamine over IV or intranasal (via the nose) is limited. Nevertheless, in the case of ketamine, oral is clearly not the “best” route, even though it may be with most typical antidepressants.

The clinical utility of IV is definitely not something to ignore — yes, they aren’t as easy to administer as a simple tablet swallowed with water, often requiring a visit to the hospital, but at the same time, for many, injections are easily the preferred form. Likewise, alternative routes beyond oral and IV also show promise in successful administration of antidepressants and other mental health medications.

Choosing the best route

Multiple routes of administration are currently available for patients in the wide field of mental health, each with their upsides and drawbacks when it comes to efficacy, speed, delivery, safety, and convenience.

Where ever possible, offering options between routes of administration along with all the information on their respective pros and cons to patients for whom, one route may be uncomfortable, unsuitable, or preferable compared to another could help massively improve patient drug compliance. Further research into patient preference and acceptability of various routes of administration for depression treatments is needed if we are to better understand the user’s perspective and what factors impact their choices.

Ultimately, continuous communication between clinician and patient throughout the process of forming a treatment plan essential so that the most suitable personalised care is provided — and how medications are delivered to the patient is a big part of it.

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