Botulinum toxin for the overactive bladder

Urinary incontinence is a major health problem and affects more patients than diabetes and heart disease combined. In UK this means many millions of patients, a lot of whom suffer in silence. A significant proportion of these patients have overactive bladders which cause them to go frequently and urgently to pass urine sometimes associated with uncontrolled leakage. This can severely affect their quality of life and restrict activities such as shopping, travelling and sports. Tablets to calm the bladder down are often ineffective and can cause side effects such as dry mouth and constipation. Patients can find them to be ineffective after a period of time and until recently, other than major surgery, there has been little to offer when tablets fail. Botulinum toxin has emerged as a new, minimally invasive and highly effective treatment for these patients.

Following ethical approval for a mechanism of action study of botulinum toxin in the bladder in 2002, a collaborative project between myself and Professor Fowler, was established at the National Hospital, Queen Square, London. At the time early results of Botox (Allergan) injections to treat neurogenic detrusor overactivity had appeared from Schurch et al in the J Urol. These patients were treated with a rigid cystoscope and needed general anaesthetic and hospital stay.

We decided to develop a minimally invasive local anaesthetic day-case technique using a flexible cystoscope and ultrafine injection needle. Initial experiments were performed on oranges under water to simulate the human bladder and subsequently patients were recruited to the study. Till date over 300 patients have been treated at Queen Square and a randomized controlled trial of Botox in idiopathic detrusor overactivity has been completed at Guy’s. A similar trial in sensory urgency is in progress and an international Phase II trial completed. The technique takes about 15 mins. A number of urological surgeons from UK and overseas have visited our centre to learn it, supported by a MS Society project grant.

Botox is equally effective in neurogenic and idiopathic detrusor overactivity refractory to first line measures such as anticholinergics. It has almost replaced the need for more invasive treatments such as neuromodulation and clam cystoplasty. It works in the human bladder primarily by down-regulating two sensory receptors – TRPV1 and P2X3. This is a prime example of reverse translational medicine.

The minimally invasive method of delivering this highly effective treatment was named the Dasgupta technique (Sahai A et al, BJUInt 2006) at the annual meeting of the British Association of Urological Surgeons, 2005.