The Good and the Potentially Risky

What are the benefits and potentially unwanted side effects of ketamine?

Benefits of IV ketamine infusion therapy

Intravenous ketamine offers several potentially powerful and useful benefits, which include rapid antidepressant effects, rapid pain relieving effects, anti-obsessive compulsive effects, and bronchodilation. It also has the added benefit of avoiding side effects typically seen in traditional antidepressatns like SSRIs.

Ketamine reduces depression and dysphoria rapidly

The amazing benefit of IV ketamins is its rapid-acting antidepressant properties. Studies strongly suggest that ketamine’s antidepressant effects are mediated by a glutamate surge that leads to a series of events that result in synaptogenesis and reversal of the negative effects of chronic stress and depression, particularly within the prefrontal cortex. Through a series of receptor blockade and activation, ketamine changes the connectivity of the prefrontal cortex of the brain to help patients reduce depression quickly.

Ketamine effectively reduces neuropathic pain

Neuropathic pain is a debilitating condition associated with traumatic, metabolic, autoimmune and neurological causes. While the causes of neuropathic pain are diverse, there are common underlying pathways. Ketamine activates immune cells in the spinal cord, as well as cause increased regulation of the N-methyl-D-aspartate receptor (NMDAR). Ketamine, a well-known NDMAR antagonist, can reduce neuropathic pain.

Ketamine dilates the breathing passages to the lungs

Ketamine is a potent bronchodilator, which means it has the added benefit of dilating the bronchi. In some cases, IV ketamine can be used to treat refractory bronchospasm as one might see in asthma. Ketamine is used in pediatric anesthesia because it has minimal effect on respiratory function and cardiovascular function, and has not been shown to be lethal in overdose.

Cases of IV ketamine overdose have not demonstrated lethality

Thus far, cases of ketamine overdose has not killed anyone who has no other substances in their system. There are cases of deaths when people overdose on ketamine and have high levels of another substance such as alcohol in their system.  A case report that helps demonstrate the non-lethality of excess ketamine involves an oral maxillofacial surgeon who inadvertently delivered 950 mg (100 mg/ml concentration) of intravenous ketamine to a pediatric patient instead of the intended 95 mg (10 mg/ml concentration). The patient did not demonstrate any systemic effects such as hemodynamic or central nervous system perturbations other than prolonged awakening. Overdose of IV ketamine causes delayed emergence from anesthesia, but is generally tolerated.

Serious side effects typically seen with other antidepressants

Antidepressant medications taken by mouth such as SSRIs and SNRIs carry significant side effects. Selective serotonin reuptake inhibitors can cause decreased libido, increased bleeding time, weight gain, sleep disturbance, and nausea and vomiting. There is also the controversial black box warning stating that antidepressants may increase the risk of suicidal thinking and behavior in some children and adolescents.

Risks of IV ketamine infusion therapy

Ketamine has common, infrequent, and rare negative side effects. The common unwanted side effects include a dissociative state in about 12% of the patients, hallucinations in about 12%, elevation in blood pressure in around 10%, and elevated heart rate in around 10% of patients. The infrequent side effect would be a reaction at the site of injection where the IV line enters the skin. The rare side effect that is listed in some references in less than 1% is nausea and vomiting.

Ketamine may cause dissociation, amnesia, and sedation

Ketamine is known to put the patient in an altered reality where the patient feels out of his or her own body, known as dissociation. This includes an unconsciousness or trancelike state where the patient exhibits minimal movement. It may also cause temporary amnesia, or difficulty recalling recent events during the infusion. These effects, which do not effect all patients, wear off after the IV infusion is finished.

Ketamine may stimulate the sympathetic nervous system

The nervous system can be stimulated by IV ketamine in a minority of patients. This would result in a slightly elevated heart rate, possibly an elevated blood pressure, as well increase energy demand. IV ketamine could increase heart and brain oxygen consumption, increase brain blood flow, and increase the pressure in the skull and eyes (know as intracranial and intraocular pressure).

Ketamine in abused amounts can cause cystitis and hepatotoxicity

In a very small percent of people who abuse ketamine over a long period of time, injury to the bladder, lower urinary system, liver, and bile duct can happen. While ketamine-induced urinary symptoms and pathology have sometimes been referred to as ketamine cystitis in the literature, the urological system of ketamine abuse affect both the higher and lower urinary tract.

Ketamine can also cause abnormalities in the biliary system with dilation and irregularity of the intra- and extra-hepatic bile ducts.  A very small percentage of patients can develop right upper quadrant pain and tenderness associated with elevations in serum alkaline phosphatase and aminotransferase levels, with minimal or no increase in bilirubin. Biliary imaging may reveal dilation and irregularity of the intra- and extra-hepatic bile ducts with fusiform dilation of the common bile duct suggestive of choledochal cysts.  Liver biopsy demonstrates changes suggestive of chronic liver obstruction or sclerosing cholangitis.  Discontinuation of ketamine is usually followed by slow and complete improvement.

In Conclusion

While there are risks associated with IV ketamine therapy, most patients tolerate the IV treatment very well. The most common side effect is feeling sedated and in a twilight sleep during the infusion. This is why our expert team gives each patients a few key medications with the ketamine infusion to help minimize the risk of having dissociative experiences. In a minority of patients, they may feel outside of their own bodies during the infusion. Remember, ketamine is a derivative of phencyclidine (PCP) which is a hallucinatory drug.

Most patients receiving ketamine infusion therapy generally tolerate it well and very few patients need to stop treatment due to side effects. That said, ketamine is a derivative of phencyclidine (PCP) which a known psychedelic drug and if not combined with sedation medications can cause hallucination in some patients. To control this dysphoria, you will be given a benzodiazepine. Other possible side effects can include nausea and more rarely, a headache. Side effects can often be managed or completely eliminated during the infusion therapy. After the completion of an IV ketamine infusion therapy treatment, patients are often tired for several hours and need to be assisted home by a capable adult. No long-term side effects have yet to be observed that can be attributed to low dose intravenous ketamine infusion therapy. Unlike other common FDA approved analgesics like opioids, ketamine is not highly addictive.