A 28-year-old female presented to Maudsley Hospital with a relapse of her treatment-resistant depression. She had a past psychiatric history of severe unipolar treatment-resistant depression, which had previously been successfully treated with ECT and medications. Her past medical history also included epilepsy, for which she was taking sodium valproate 600mg with good effect.
She was already on a combination of antidepressant medications, mood stabilisers and an antipsychotic. Her medication regime included: Vortioxetine 20mg, Levothyroxine 150mcg, Lithium (Priadel) 800mg, Valproate 600mg and Quetiapine 500mg.
Up until this relapse, her mood had been stable and she had been taking her medications as prescribed.
On assessment, she was well-dressed and well-groomed. She spoke slowly and monotonously with one syllable words and appeared dysthymic in nature. On discussion, it was evident that she had negativistic cognitive distortions and ideas of worthlessness. She was at times not fully able to engage in the assessment but was generally coherent. There were no signs of hallucinations or abnormal sensory experiences, but she did appear more depressed than previously and more easily distracted.
Due to this relapse, ketamine augmentation therapy was started on 25/10/2021 in the form of sublingual lozenges 160mg twice weekly. This was increased to three times a day on 10/01/2022 with good effect. However, she complained of nausea and vomiting from the sublingual preparation.
In September 2022, her depression began to decline again and on 27/09/2022 the treatment was switched to oral capsules 240mg and escalated to four times a week. She reported that the nausea and vomiting improved significantly.
The ketamine showed excellent anti-depressant response. However, she began to complain of symptoms of dysuria which initially began insidiously. She described this as “stinging during and after peeing”. This discomfort could occasionally last for a few hours after voiding. These usually happened 12–24 hours after taking the ketamine dose. She was managing the pain with over-the-counter paracetamol and phenazopyridine hydrochloride, which she found very helpful. She was advised to stay well hydrated whenever taking the ketamine and to continue monitoring her symptoms closely. She reported taking the ketamine exactly as prescribed.
Unfortunately, the frequency and severity of the dysuria progressively worsened. A urine microscopy, culture and stain demonstrated sterile pyuria, with positive inflammatory cells, but no growths, nitrites or blood. No intimate examinations were performed. There were no indications of a urinary tract infection or a sexually transmitted infection.
Blood tests were unremarkable and renal function was normal. This included: Na 141mmol/L, K 4.7mmol/L, urea 3.2mmol/L, creatinine 80mmol/L, GFR 89, WCC 5.2 x109/L
Due to the concerns about irreversible bladder and renal tract injury, the decision was made to withdraw the ketamine. The patient reported that within 3 weeks, the symptoms of dysuria had completely resolved, but her mood had worsened. A repeat urine test carried out yielded normal results. A decision was made to begin ECT and to rationalise her medications, which included discontinuing the ketamine.
Patient perspective
The ketamine was really helpful for my mood – it worked quickly and my family, friends and I all saw the difference straight away. My mood was better, I had more energy and motivation to do things, my thought processes took a more positive swing and I was actually genuinely happy to be alive again. Sadly, the urinary symptoms were horrible – they felt like a really bad urinary tract infection and the pain lingered longer each time. In the end, the urinary symptoms made me start to dread taking each dose of the ketamine, as I knew that the pain would be there for most of the day/night afterwards. As a result, making the decision to stop the ketamine was a difficult decision, but so was the idea of continuing it.