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>Hello folks >This email started off as a short answer to some of Ida's comments in her >email of 30 Jan., but as I dealt with each point, I began to wonder if there >may be a greater area of misunderstanding in the way we take levodopa than >I first thought. I really need to hear from you on this subject, so please >write. > > Brian You might like to see a bigger extract from the Algorithm about diphasic diskinesia. Here we go; DYSKINESIAS. Dyskinesias can be drug or disease-related. If they include a prominent component of chorea, medications are implicated. If they are exclusively dystonic, this could either be caused by a disease-related condition or secondary to medications. Thus, dyskinesias an more appropriately addressed by separating them into those that are choreiform/choreodystonic vs those that are exclusively dystonic.(breakout 18). Choreiform /choredystonic. Chorea in the context of PD is invariably related to medications, Frequently, a prominent dystonic component is seen in conjunction with the chorea; hence the term, "choreodystonic." These choreodystonic dyskinesias occur in two patterns. The most common form is seen at the time of peak levodopa effect and has been termed "peak-dose dyskinesia" (or I-D-I response, a shorthand for "improvement-dyskinesia-improvement").[124] The first and most obvious approach to this problem is to modestly lower the individual uses of carbidopa-levodopa (eg, 25-mg decrements), Unfortunately, many patients have a very narrow therapeutic window, and even a small levodopa decrement can result in transition from a dyskinetic state to a relative "off" state. In this circumstance, one may consider adding or increasing a dopamine agonist medication (bromocriptine or pergolide), which allows a slightly tighter titration of the response. Patients who swing dramatically from severe dyskinesia and who have a short-duration response to the "off" state may find liquid carbidopa-levodopa to be a better option, with benefits and drawbacks as described above. Choreodystonic dyskinesias are also seen in a second distinct pattern, in which these adventitious movements occur just at the beginning and again at the end of the levodopa response cycle. This has been termed "diphasic dyskinesia" or D-I-D response, a shorthand for "dyskinesia-improvement-dyskinesia").[124] This pattern is much less common than peak-dose dyskinesia and is often difficult to diagnose because the pattern may not he obvious, either to the patient or the clinician, The end-of-dose period of dyskinesias is typically more prolonged and troublesome than the initial dyskinetic period of the levodopa cycle. Although this D-I-D pattern can be very difficult to treat, it may respond to simple measures if the dyskinesias are relatively mild. First, more frequent dosing of carbidopa-levodopa may allow a more continuous "on" state without periodically cycling through the dyskinetic phases. Obviously the timing of the doses should he based on the carbidopa-levodopa response duration. In a similar strategy to the one for treating "wearing-off" problems, a sustained-release formulation of carbidopa-levodopa may be substituted for the standard formulation, The addition of dopamine agonist therapy close titration, using liquid carbidopa-levodopa, may be options for some patients. Finally, subcutaneous apomorphine may provide a route of escape from the dyskinetic phase. The use of subcutaneous apomorphine (as described before) allows time for the next dose of carbidopa-levodopa to become clinically effective. Occasional patients experience severe choreodystonic dyskinesias with a diphasic pattern, this can be very difficult to treat effectively. The initial descriptions of this clinical pattern[124] documented the failure of carbidopa-levodopa dosages administered at short intervals around the clock to effectively treat this problem. Although several carbidopa-levodopa doses at short intervals can successfully defer the end-of-dose dyskinetic period, this strategy fails after approximately tour to five overlapping doses.[124] At this point, patients typically begin to experience a sense of drug intoxication and, furthermore, note a decreasing threshold for dyskinesias with an inability to suppress them, despite even larger doses of carbidopa-levodopa. For the diphasic dyskinesia pattern to become obvious, the levodopa dose must be adequate; too low a dose will simply result in dyskinesias, whereas a higher dose allows the full pattern to develop[124] The usual dosages of carbidopa-levodopa used to treat conventional parkinsonian motor problems are adequate for demonstration of the diphasic dyskinesia pattern (ie, 100 to 250 mg of levodopa). Typically, it is the end-of-dose dyskinetic period rather than the initial dyskinetic phase that is the more troublesome and sustained. It tends to occur at a fairly well-defined portion of the levodopa response cycle, usually 2 to 8 hours after a single dose of carbidopa-levodopa. One treatment strategy is to overlap four to five doses of carbidopa-levodopa at intervals that are just long enough to preclude the development of the dyskinetic phase at the end of each dosage cycle[124] After the last dose, however, patients will cycle through the dyskinetic phase but at a relatively predictable time. Thus, they can arrange to be at home-and perhaps self administer a mild, short-acting tranquilizer such as alprazolam--during the time the dyskinetic period is expected. Once they have cycled through this dyskinetic period, patients typically experience adequate control of their parkinsonian motor symptoms for the remainder of the day, although control is not quite as good as during the time of peak levodopa response. This control typically continues overnight and into the next morning. If left untreated, patients usually start to experience increasing motor manifestations of parkinsonism by mid to late morning, at which time they can again restart their levodopa cycle, taking four to five overlapping doses. Thus, with this strategy patients can attain good control of their parkinsonian symptoms for several midday hours and adequate control during other portions of the day, once they have cycled through their last dyskinetic period. An alternative strategy for treating the severe diphasic choreodystonic dyskinesias is to switch the patient to dopamine agonist monotherapy (bromocriptine or pergolide). The transition can be difficult, as the dopamine agonist must be slowly introduced and the carbidopa-levodopa dosages concomitantly decreased. Eventually, as patients make the transition to bromocriptine or pergolide alone, they often will find that their parkinsonism is not as well controlled as with carbidopa-levodopa. The dyskinetic periods may be absent or substantially reduced in severity, however. To be effective, the bromocriptine or pergolide doses usually need to be higher than those employed when these drugs are used as adjunctive therapy with carbidopa-levodopa. For monotherapy, the usual range is 30 to 60 mg of bromocriptine or 3.0 to 6.0 mg of pergolide as monotherapy. Exacerbated by anxiety. Regardless of the type or pattern. choreodystonic dyskinesias can be unmasked or worsened by anxiety- provoking situations. If this is a frequent problem for the patient, intervention directed at neuropsychiatric issues may be appropriate. My own dyskinesia appears to be of the diphasic type.Unfortunately my drug routine is a bit messed up at present as I've had a drug holiday for a week so can't send you any typical figures.I'm shortly going on a real holiday for three weeks and hope to contribute to this correspondence on my return. David Langridge.