Repeated ketamine injections in synergy with antidepressants for treating refractory depression: A case showing 6-month improvement

This case study (2019) explores repeated intravenous (IV) ketamine in synergy with antidepressants to treat refractory depression (TRD). It found that high-dose IV ketamine may stably enhance depressive symptoms and cognitive function in patients with TRD who do not tend to respond to a rapid intravenous dose of standard-dose ketamine.

Abstract

“What is known and objective: Some patients with refractory depression who fail to respond to rapid injection of standard-dose ketamine are injected with high doses, but the safety and efficacy of this practice are unclear.

Case description: A 57-year-old woman with refractory depression whose symptoms did not improve after 20-seconds intravenous injection of 0.5 mg/kg ketamine went into remission following eight, 1-minute intravenous injections of 1 mg/kg ketamine delivered over a 4-week period. By 6-month follow-up, no significant adverse events had occurred and cognitive function had improved.

What is new and conclusion: High-dose intravenous injections of ketamine may stably improve depressive symptoms and cognitive function in patients with refractory depression who do not respond to rapid intravenous injection of standard-dose ketamine. The high-dose treatment appears to be associated with only mild side effects.“

Authors: Min Wang, Zhenzhen Xiong, Bin Su, Lan Wang, Zhixiong Li, Yali Yang, Jing Fang & Zhe Li

Summary

Ketamine can rapidly improve depressive symptoms, and a rapid injection of 0.75 mg/kg is more effective than standarddose of 0.5 mg/kg.

Some patients with refractory depression are injected with high doses of ketamine.

A 57yearold woman with refractory depression went into remission following eight injections of 1 mg/kg ketamine over a 4-week period.

Highdose ketamine injections may improve depressive symptoms and cognitive function in patients who do not respond to standarddose ketamine.

Highdose intravenous ketamine injection safely managed TRD for at least 6 months, but chronic, longterm use of ketamine can produce serious side effects, such as addiction and cognitive impairment.

2 | CASE DESCRIPTION

A 30 year old Chinese woman was hospitalized for depressive disorder in 1992, but was discharged after 120 days of treatment. She recurred in 1993, but had good support from family members and did not experience any adverse life events.

In 2018, she took several pills of amitriptyline in an effort to commit suicide. She reported feeling no meaning in her life and a desire to jump from a tall building.

The patient’s results were within normal limits for routine blood tests, blood biochemistry, thyroid function, electrocardiography, chest radiography, cardiac function, gynecology, abdominal colour Doppler ultrasound and magnetic resonance of the head. She was diagnosed with recurrent depressive disorder.

A patient with major depression was treated with venlafaxine release capsules and escitalopram tablets. Ketamine therapy did not improve her symptoms, and she was observed for 1 hour in the operating room without abnor mality.

The patient received two intravenous injections of ketamine per week over 4 weeks, and her depressive symptoms were reduced by nearly 50% after two injections. However, she relapsed the next morning, but her depressive symptoms became less severe after the third injection.

Ketamine is known to act as a noncompetitive antagonist of the NMDA glutamate receptor, but how exactly it acts against TRD is unclear. We treated our patient with 0.5 mg/kg ketamine over 20 seconds, and 1 mg/kg ketamine over 1 minute, and she experienced remission for 6 months.

We suspect that the combination of ketamine and antidepressant medications improved our patient’s symptoms of TRD, and the improvement was sustained for up to 4 weeks. Ketamine may have decreased damage to different domains of cognition, and venlafaxine may have contributed to the improvement.

3 | WHAT IS NEW AND CONCLUSION

This case report suggests that administering 1 mg/kg ketamine during 1 minute can significantly improve depression, anxiety and cognitive dysfunction in TRD.