>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.