Ketamine has been in the news recently as it is increasingly being prescribed for treating depression and anxiety. Research into this potential use of ketamine has been conducted for at least 20 years however clinical use has only recently become more widespread. Clinics are now offering ketamine sessions for patients who are suffering from treatment-resistant depression and many patients are talking about its benefits.
Depression and Anxiety
Depression is defined as chronic, sometimes episodic, symptoms of low mood, sadness, guilt, lack of motivation, and anxiety. It may be combined with manic episodes in some patients. Current antidepressant medications can show benefit within a few weeks after initiating treatment. However not all patients respond well to these medications and nearly one third of patients do not achieve a recovery with drug intervention. Finding effective treatments for depression is essential as it is estimated that up to 15% of individuals worldwide may be diagnosed with it.
When it comes to the pathophysiology of depression, N-methyl-D-aspartate receptors (NMDAR) are a key concern of research as they have been implicated in an increase in glutamate. As one article on this topic clearly states, “the NMDA receptor complex may be involved in the behavioral deficits induced by inescapable stress and … substances capable of reducing neurotransmission at the NMDA receptor complex may represent a new class of antidepressants.”
This is why the non-competitive voltage-dependent NMDAR antagonist ketamine has been studied and found to be effective at treating depression. A single sub-anesthetic dose of ketamine has been found to have rapid, significant effects in patients with treatment resistant depression.
Various metanalyses of studies of ketamine used for treating depression have found that it performs better than placebo at 1 hour, 1 day, 3 days, and 1 week after treatment. Treatment with ketamine produces rapid results – much faster than those achieved with typical antidepressants. For most patients, efficacy is achieved within the first hour after administration. Some patients may experience antidepressant effects for up to 2 weeks.
Ketamine Drug Forms
Typically ketamine is used intravenously in clinics that use it to treat depression. This form of ketamine, which was originally approved for anesthetic purposes, is the one that is commercially available. Recently a nasal spray form of the drug has also been approved. There are a few reasons why intravenous administration is not ideal for this treatment. As a psychiatric treatment, intravenous injection requires the patient to be in the office. This may be beneficial for the treatment so that it can be monitored. However it does limit the continued use of the medication.
Many patients may be hesitant to get an injection due to an anxiety about needles. Other dosage forms may make the treatment experience easier for both the patient and practitioner. Oral and sublingual forms of ketamine have been researched for efficacy, safety, and feasibility in treating depression.
Different forms of ketamine can provide benefits compared to the currently available drug forms. Research shows that various forms of ketamine can be used for treating anxiety and depression including sublingual forms, oral forms, and nasal sprays. Sublingual administration with a solution or troches allows for rapid absorption without the need for an injection. An effective dose can be obtained in a way that is easier for the patient.
The bioavailability of different drug forms varies. For example, it is well documented that when taken orally ketamine has low bioavailability. However that does not mean it cannot be used therapeutically. Many drugs that have low oral bioavailability are still used, just with higher dosages to compensate for the low percentage that is absorbed.
Topical forms can be used for treating certain types of pain that are refractory to other treatments. In the form of a topical cream, ketamine has been studied for its analgesic properties for treating neuropathic pain. Topical creams can be applied directly to the area of concern without significant systemic effects.
More Benefits of Compounding
Compounding does not just open up possibilities for new drug forms but also allows for greater customization of dosing strengths. Psychiatrists are familiar with titrating doses of antidepressants and other medications. A compounding pharmacy is able to provide a medication like ketamine in any dosage required, allowing for individualized titration. The patient’s dosing can be adjusted by small amounts if that is what is deemed necessary by the prescriber.
Most compounding pharmacies work with you on a more personal level than your typical retail pharmacy or drug supplier. A lot of this has to do with the way that each prescription is made individually for the patient. A retail pharmacy can only offer what is being manufactured. The level of customization available with a compounding pharmacy is often underutilized and underappreciated.
Articles
Ketamine and depression: a narrative review – Drug Design, Development, and Therapy
Functional antagonists at the NMDA receptor complex exhibit antidepressant actions – European journal of pharmacology
Oral Ketamine for Depression, 1: Pharmacologic Considerations and Clinical Evidence – The Journal of Clinical Psychiatry
Mechanisms of Ketamine Action as an Antidepressant – Molecular Psychiatry