Many of the symptoms of Parkinson’s disease relate to a gradual reduction in the ability of the brain to produce a critical chemical know as dopamine. Indeed this discovery and the subsequent development of medications which increase brain dopamine (dopamine replacement therapy) have remained the mainstay of medical treatment of Parkinson’s disease since the 1970’s.
Tablet formulations of Dopamine replacement therapy (DRT), taken alone or in combination with one another, reliably improve most motor and some non-motor symptoms of Parkinson’s disease.
Whilst medications may take weeks to take effect after a diagnosis of PD, and some months of fine tuning to achieve optimal benefit, DRT usually results in a substantive and consistent improvement in motor (and some non-motor) symptoms. In this phase, people living with PD need to take DRT medications between one and four times per day. Provided patients continue to take their medication, this treatment benefit typically persists for years, often with little need to adjust therapy.
Over time however, the duration of treatment benefit from individual medication doses shortens, such that patients begin to notice a recurrence of motor symptoms – slowness, stiffness, tremor or walking difficulty towards the end of each dose, only to notice a resolution of symptoms as the next dose becomes effective. This is known as end of dose wearing off. When this occurs with increased frequency, this variability in symptom control is termed motor fluctuations.
Around this time, some patients also develop excessive and involuntary movements termed dyskinesia.
Initially motor fluctuations and dyskinesia typically respond to manipulations in tablet therapy, such as increasing dose frequency or adding in alternate dopamine replacement therapies. Further adjustment of medication regimes may be required over the following months or years to maintain consistency of medication response.
With further progression of PD however motor fluctuations and dyskinesias can become more inconsistent and unreliable. At this stage manipulations in tablet therapy tend to be ineffective in achieving consistent control.
Here a second tier of therapies including apomorphine, Duodopa and Deep Brain Stimulation can be very effective in achieving more consistent control of physical symptoms.