OFF episodes: 4 types and their potential impact on your patients

OFF episodes occur in the majority of patients with PD.1 During OFF episodes, patients experience a change in their clinical state, as motor and/or non-motor symptoms return or worsen.2

Not all OFF episodes are the same.

As part of a complete clinical assessment, it is important to look beyond end-of-dose wearing-off and to recognize that there are 4 types of OFF episodes and understand how they each can impact a patient with PD.

  1. Morning OFF (morning akinesia)

    Patients may: awaken in an OFF state in the morning prior to taking their first dose of antiparkinsonian medication; or experience an OFF after waking and either have a delayed ON or No On.3

    “Sometimes I have symptoms when I wake up, on other days it doesn't take long for my symptoms to reappear.”

    Statements aggregated from research and interviews.

  2. Wearing OFF

    End-of-dose deterioration and recurrence of symptoms, possibly as a result of shorter duration of benefit of antiparkinsonian medication.4

    “I feel as if the medication is draining out of my body before I take my next dose.”

    Statements aggregated from research and interviews.

  3. Delayed ON, Partial ON, No ON (dose failure)

    A delay in symptom improvement, less-than-optimal symptom improvement, or even no symptom improvement from an antiparkinson medication dose, as compared with their normal medication response.5-7

    “Even after taking meds, I’m noticing that I’m still slow and can’t keep up. Sometimes it takes a while for my medication to work or I don't feel it kick in at all.”

    Statements aggregated from research and interviews.

  4. Unpredictable OFF

    Sudden and random changes from an ON to marked OFF symptoms over seconds or minutes.3,6

    “I feel like my symptoms are pretty much under control —and then all of a sudden it seems like my medication stops working.”

    Statements aggregated from research and interviews.

Response fluctuations in levodopa-treated PD1,8

Dyskinesia

ON Time

OFF Time

Response Fluctuations in levodopa-treated PD
*

Levodopa is the gold standard of PD treatment. As the disease progresses, patients can experience OFF episodes. The typical levodopa plasma concentration for initiating reversal of parkinsonian effect is in the range of 800 to 1,100 ng mL.9

Morning and Unpredictable OFF episodesmay be troublesome and problematic for patients

Morning OFFs (morning akinesia) may delay the start to a patient’s day

  • As PD progresses, patients can experience OFF episodes. Patients who are affected by morning OFFs (morning akinesia) experience a wearing off of their last nighttime dose and/or report a delayed effect of their initial morning dose of antiparkinsonion medication, possibly prolonging the OFF state3
  • Morning OFFs (morning akinesia) may impact activities of daily living and may be difficult to manage3, 10

60% of patients reported experiencing morning OFFs (morning akinesia) in a clinical trial of patients with a mean PD duration of 7 years (N=320)†11

Results from a multicenter, observational study in patients with PD across all disease stages, with symptoms assessed using the UPDRS, PDSS visual analogue scale, and the NMSQuest self-assessment screener.


Unpredictable OFFs may be frustrating and challenging for patients

  • Patients experiencing an unpredictable OFF may transition suddenly from being ON to OFF within minutes or even seconds6
  • Unpredictable OFF periods can usually be characterized as severe (ie, patients may be very disabled in regard to motor function)5
  • Because unpredictable OFFs are unexpected, they can be much more difficult to prevent and thus treat because they are not related to a patient’s level of aniparkinsonian medication, and may result in motor and non-motor complications, including anxiety, stress, and embarrassment5,6

36% of patients reported experiencing unpredictable OFFs in a small study of motor complications (N=143) in patients with a mean disease duration of 9 years.10,‡

Patients were assessed using the Hoehn and Yahr scale, the motor part of the UPDRS, and a PD-specific quality of life questionnaire (PDQ-39).

References

  1. Hametner E, Seppi K, Poewe W. The clinical spectrum of levodopa-induced motor complications. J Neurol. 2010;257(suppl 2):S268-S275.
  2. Chou KL, Stacy M, Simuni T, et al. The spectrum of "off" in Parkinson's disease: What have we learned over 40 years? Parkinsonism Relat Disord. 2018 doi: 10.1016/j.parkreldis.2018.02.001. [Epub ahead of print]
  3. Obering CD, Chen JJ, Swope DM. Update on apomorphine for the rapid treatment of hypomobility (“off”) episodes in Parkinson's disease. Pharmacotherapy. 2006;26:840-852.
  4. Jankovic J. Motor fluctuations and dyskinesias in Parkinson’s disease: clinical manifestations. Mov Disord. 2005:20(suppl 11):S11–S16.
  5. Adler CH. Relevance of motor complications in Parkinson's disease. Neurology. 2002;58(4 suppl 1):S51-S56.
  6. Olanow CW, Stern MG, Sethi K. The scientific and clinical basis for the treatment of Parkinson disease. Neurology. 2009;72(suppl 4):S1-S136.
  7. Reimer J, Grabowski M, Lindvall O, Hagell P. Use and interpretation of on/off diaries in Parkinson's disease. J Neurol Neurosurg Psychiatry. 2004;75:396-400.
  8. Pahwa R, Lyons KE. Levodopa-related wearing-off in Parkinson's disease: identification and management. Curr Med Res Opin. 2009;25:841-849.
  9. LeWitt PA. Levodopa therapy for Parkinson’s disease: pharmacokinetics and pharmacodynamics. Mov Disord. 2015;30:64-72.
  10. Chapuis S, Ouchchane L, Metz O, Gerbaud L, Durif F. Impact of the motor complications of Parkinson’s disease on the quality of life. Mov Disord. 2005;20:224-230.
  11. Rizos A, Martinez-Martin P, Odin P, et al. Characterizing motor and non-motor aspects of early-morning off periods in Parkinson's disease: an international multicenter study. Parkinsonism Relat Disord. 2014;20:1231-1235.