Posted by Sunnely on July 15, 2000, at 17:16:26
In reply to Re: Risks of developing TD » Sunnely, posted by SLS on July 15, 2000, at 11:36:21
> Thank you for posting such a comprehensive, organized, and well documented review regarding TD.
Thanks for those kind words.
--------------------------------------------------> I recently bumped into one study that's statistics indicated that it was not age that was the associative factor, but rather the number of years on the medication. They concluded that it was the elderly population that have been taking neuroleptics the longest.
As I have mentioned in my previous post, both age and duration of neuroleptic treatment are considered among the risk factors for TD. (Reference: Tardive Dyskinesia: A Task Force Report of the American Psychiatric Association. American Pwsychiatric Association Press, Washington, DC, 1992.)The study you bumped into is correct but does not paint the whole picture. FYI, the usual onset of schizophrenia is at late teens to 20s. (Earlier onset with males than females.) If these people start receiving neuroleptics at this age range, in 40 to 50 years they would be considered elderly and therefore high risk for TD (elderly with 40-50 years exposure to neuroleptics). However, if you compare the risk of TD on a person in his/her 20s receiving neuroleptic for the first time and an individual in his/her 60s receiving neuroleptic for the first time, the chance of TD developing and at much earlier stage is much higher in the latter.
The risk of TD remains fairly stable through ages 20 to 40, then rises considerably. TD is 3 times higher in people over age 40 than under 40. Postmenopausal women have a higher risk for TD than premenopausals. (The female hormones may have some protective factor.) This risk continues to rise until about age 70 when the risk of TD in women becomes similar to that seen in men.
The bottom line here is, the older a person is when he/she first receives neuroleptic, the more likely he/she is to develop TD early in treatment. Not only does TD occur earlier in the elderly, it is more severe and persistent in this age population.
--------------------------------------------------> Employing drug holidays had been the standard practice years ago, but we now know that this actually increases the risk of developing TD many fold.
Exactly. There were 2 types of maintenance treatment strategies with neuroleptic: 1) Continuous "low-dose" neuroleptic treatment, and 2) Intermittent or "targeted" neuroleptic treatment strategy. With the first strategy, neuroleptic is administered continuously but at doses that are lower than those conventionally used used to treat psychotic symptoms. With the second strategy, patients require neuroleptic medication ONLY during time of symptom exacerbation. One of the drawbacks found with the intermittent treatment strategy is that, there appears to be a correlation between the number of on/off cycles of medication and incidence, severity, and persistence of TD. Needless to say, the second treatment strategy was subsequently abandoned.
--------------------------------------------------> Are blood-levels of neuroleptics ever used clinically?
Yes, but not routinely. For many drugs, determining blood levels are not available or reliable. As much as 100-fold variation in blood levels among patients receiving the same dose of neuroleptics have been recorded. For others, blood levels have little relationship to clinical effects. Some drugs have several metabolites that just complicate the picture.There are at least 2 neuroleptics, I am aware of wherein determining blood levels are beneficial: haloperidol and clozapine. It was suggested that there is a curvilinear (inverted "U" shape or bell-shape) relationship between the blood level of haloperidol and clinical response. (Sometimes this is called "therapeutic window.") The late Dr. Van Putten suggested a haloperidol blood level range of 5-12 ng/ml although some consider an optimal range of 4 to 25 ng/ml. What this curve means is that, anything below and above the suggested blood level range leads to poor response. Higher levels lead to loss of antipsychotic effect but continued rise in side effects. Of course, this is not etched in stone. In some patients, their psychosis only remit with higher blood levels. (Reference: Clinical Use of Neuroleptic Plasma Levels by Marder SR, Davis JM, and Janicak PG. American Psychiatric Press, Inc., Washington, DC, 1993.)
Clozapine is another drug where blood level determinination is considered beneficial. Clozapine experts like Perry PJ and others, recommend a "therapeutic" blood level of at least 350 ng/ml. Again, this is not etched in stone. A number of patients on Clozaril do well with blood levels less than 350. Another occasion where clozapine blood level is beneficial is in situation where you would like to avoid a serious side effect. Patients with clozapine blood levels higher than 1000 ng/ml are at high risk for seizures. Rising clozapine blood level can happen when another drug that inhibits the metabolism of clozapine is added. For example, Luvox is a marked inhibitor of CYP1A2 (main metabolic pathway of clozapine).
Determining blood levels of a neuroleptic is helpful in the following situations:
1) Distinguishing between side effects and psychosis.
2) Drug-drug interactions.
3) Suspected noncompliance.
4) When toxicity is suspected.
5) In elderly or medical ill, monitor side effects.
6) To document the level of a therapeutic dose for an individual patient, especially those requiring unusually high or low doses (may be helpful in legal cases).
7) To expedite rapid treatment of suicidal or homicidal patients.
8) Help define the dose-response relationship.
9) Provide objective data when there is paucity of hard information.
10) Determine if there has been an adequate trial.
11) Determine if the patient responded to the active drug or had a placebo response.
12) Determine if the benefit outweighs the potential for adverse effects.
13) Minimize cost. (a) Noncompliance and subtherapeutic blood levels ----> delay remission of schizophrenic condition ----> prolongs hospital stay or additional outpatient visits. (b) Identifying excessive blood levels ----> avoids toxicity ----> avoids unnecessary or prolonged hospitalization (and additional laboratory work up).
poster:Sunnely
thread:40349
URL: http://www.dr-bob.org/babble/20000708/msgs/40580.html