Levodopa
| Type | Recommendation |
|---|---|
| When to deprescribe | |
| CBR |
We suggest deprescribing decisions be made in consultation with the individual, their carer/family members, and their GP and/or specialist providersneurologist to ensure it aligns with their preferences, goals and overall treatment plans. We suggest deprescribing be offered to older people taking levodopa when:
|
| Ongoing treatment | |
| CBR | We suggest continuing levodopa if the benefits (e.g. motor or non-motor) clearly outweigh the potential risks (e.g. fall risk, orthostatic hypotension and sedation); however, we suggest reassessing the need for long-term therapy periodically and monitoring for emerging risks and benefits. |
| How to deprescribe | |
| CBR |
We suggest levodopa may be ceased abruptly (e.g. when there is a need to rapidly assess levodopa responsiveness or in the presence of significant toxicity) or gradually tapered by reducing the dose by one tablet or 100 mg every two weeks until it is fully withdrawn (e.g. for people on high baseline daily doses), ensuring individuals remain symptom-free before initiating each tapering. |
| Monitoring | |
| CBR |
We suggest closely monitoring for worsening motor (e.g. tremors, bradykinesia, rigidity) and non-motor symptoms (e.g. mood changes, cognitive decline) such as every one to two weeks. |
CBR, consensus-based recommendation
Parkinson's disease
Levodopa is the most effective and commonly used treatment for the motor symptoms of Parkinson's disease. However, its dosage often requires careful adjustment based on the individual's condition and response. The prescribed dose must balance treatment benefits (both motor and non-motor) against potential dose-limiting side effects. This balance becomes increasingly complex in advanced Parkinson's disease and in older people with comorbidities such as dementia. Levodopa-induced complications, including increasing dyskinesia duration, more disabling dyskinesia as well as longer, more sudden and unpredictable OFF periods, had significant adverse impacts on the quality of life of people with Parkinson's disease [602].
Restless legs syndrome (RLS)
Levodopa may be prescribed with a dopamine decarboxylase inhibitor as needed to treat intermittent RLS symptoms (i.e. symptoms occurring less than once or twice a week). It is not recommended as a chronic treatment due to the high risk of tolerance and augmentation. Augmentation is a serious adverse event described as the “onset of RLS symptoms earlier in the day after an evening dose of medication, the spread of symptoms to the arms, paradoxical worsening of symptoms with dose increase, and shorter effect of each dose of medication” [603, 604].
Refer to the narrative evidence summary, the GRADE Summary of Findings table in the guidelines, and the Technical Report for a complete presentation of the deprescribing evidence based on the GRADE framework (including other factors considered in developing the recommendations).
Although levodopa can reduce fall risks in some people by addressing specific gait issues, levodopa may induce or worsen orthostatic hypotension in more than half of people which in turn increases fall risks [605, 606]. Additionally, levodopa may cause sedation and daytime somnolence, thereby increasing the risk of falls [607, 608].
Given the potential risks associated with long-term use of levodopa, deprescribing may be considered appropriate if side effects are intolerable or there has been no clinically meaningful improvement. In contrast, for people who continue to receive meaningful therapeutic benefits and the risks are tolerable, levodopa should be continued with periodic monitoring for emerging risks and benefits.
We identified two studies (one RCT and one before-and-after study) related to levodopa deprescribing [609, 610].
Overall, the current evidence of outcomes arises from only two studies of very small sample sizes and are of low and very low certainty due to methodological limitations. The evidence at this stage is inadequate to inform evidence-based recommendations.
If levodopa is considered appropriate to deprescribe, it may be appropriate to closely monitor for worsening motor (e.g. tremors, bradykinesia, rigidity) and non-motor symptoms (e.g. mood changes, cognitive decline).
Key study characteristics and results
A narrative summary of each study is provided below, highlighting key characteristics and main findings.
Tse 2008 conducted an RCT that included 11 nursing home residents who are currently treated with levodopa and not taking any other medicines for Parkinson’s disease for the past 30 days [610]. Participants were included if they had advanced Parkinsonism (presence of bradykinesia and at least one of the following: rest tremor, rigidity, or postural instability) and dementia (MMSE < 19). Participants with current or past treatment with antipsychotics, stroke, or history of central nervous system structural lesions were excluded. Residents were randomised to levodopa continuation (n=5) or discontinuation (n=6). At week four, there was no significant difference between the two groups in terms of cognition (MD 3.20, 95% CI -7.80, 14.20) or motor and non-motor symptoms evaluated using the Unified Parkinson's Disease Rating Scale (MD -11.99, 95% CI -39.98, 16.00).
Hauser 2000 conducted a before-and-after study that included 31 community-dwelling older people with early Parkinson's disease (Hoehn and Yahr stage one to three) who previously participated in RCT to determine the effects of selegiline, levodopa, and bromocriptine on the progression of Parkinson's Disease [609]. Participants were included if they had at least two of three cardinal features of Parkinson's Disease (bradycardia, rigidity, resting tremor) and participants with a history of exposure to neuroleptic medicines were excluded. Comparing day one to day 15, discontinuation of levodopa/carbidopa and bromocriptine led to a reduction in the total Unified Parkinson's Disease Rating Scale scores (± standard error) by 7.4 ± 1.5 (p < 0.0001) in all participants. During deprescribing, none of the participants reported complications other than worsening Parkinsonian symptoms.
In the RCT, the levodopa dose was tapered by one tablet (or 100 mg) every three days until completely withdrawn (low certainty; n=11) [610]. The method of deprescribing was not described in the before-and-after study (very low certainty; n=31) [609].
Levodopa may be gradually tapered by reducing the dose by one tablet or 100 mg over several weeks, particularly for people on high baseline daily doses. However, when there is a need to rapidly assess levodopa responsiveness or in the presence of significant toxicity, it may be more appropriate to cease levodopa abruptly without the need for tapering.