chemamr
Moderator and PGY2
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A
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Any time something is written against me, I not only share the sentiment but feel I could do the job far better myself.
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| goodyear
Forum Guru
Topics: 16
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I think I read somewhere.. it's Flouxetine
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| bikerdoc
Forum Senior
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Haloperidol
Since the 1960's, haloperidol (Haldol) has been the mainstay of treatment for TS. During the first years of its use, dosage was rapidly increased to very high levels followed by gradual reduction. However, it is now accepted that haloperidol is most effective at quite low doses, and patients generally are started at 0.25 to 0.50 mg/day and slowly increased every 4 to 5 days up to an average of 3 to 4 mg/day. Impressive benefits are seen at those low doses, and patients may have almost complete remissions with few side effects. Some may benefit from as little as 1 mg/day or less. Those who do not respond to low doses of haloperidol may sustain a reduction of symptoms at higher doses (10-15 mg), but results are never as satisfying and side effects intervene to limit the drug's usefulness.
Up to 80% of patients with TS initially benefit from haloperidol, sometimes dramatically. However, our long-term follow-up suggests that only a smaller number, perhaps 20-30%, continue haloperidol for an extended period of time. Patients often discontinue the drug because of the emergence of side effects (including excessive fatigue, weight gain, dysphoria, parkinsonian symptoms, intellectual dulling, memory problems, personality changes, feeling like a "zombie," akathisia, school or social phobias, loss of libido, sexual dysfunctions, and, especially after chronic use of high doses, tardive dyskinesia [TD]). There is a diversity of opinion about the use of anti-parkinsonian agents with haloperidol.
Some clinicians prefer to initiate treatment with both haloperidol and low doses of anti-parkinsonian medication (e.g., 0.5 mg/day of benztropine). Others will not use anti-parkinsonian medication until side effects warrant them. Most parkinsonian and acute dystonic reactions can be controlled with 1-2 mg/day of benztropine or an equivalent medication. Akathisia may be harder to manage.
School phobias generally appear during the first weeks of treatment with low doses of haloperidol even while the tic symptoms are improving. Social phobias and dysphoria in adults may involve acute anxiety about going to work or performing at work and can be extremely disabling. When such phobias are not recognized as drug side effects, they can continue for months; they remit within weeks of haloperidol discontinuation. Intellectual dulling leads to marked worsening of school and work performance. Children who are "A" students and have friends may become "C" students, dysphoric, and isolated.
The long term use of medication often complicates the understanding of the emergence of social and personality difficulties. Side effects of neuroleptics may have considerable impact on a child's sense of self-control, autonomy, self-esteem, and cognitive and social competence. In addition to the way that psychoactive medication may alter how a child's body feels to him or her and how he or she experiences the working of his or her mind, the use of any medication may single out a child in school, alter the daily schedule, focus parental and other adult concern on small changes in symptoms and side effects, and tie down the child to the care and attention of many adults.
Education of the patient and/or family about the possibility of developing TD is essential, as are periodic assessments for dyskinetic movements that the patient or family may mistake for TS symptoms. Because of the frequency and potential gravity of side effects associated with haloperidol, many clinicians experienced in the treatment of TS prefer to try other medications first and reserve haloperidol for more severe and refractory cases.
It should be emphasized that withdrawal from haloperidol and other neuroleptics may produce confusing symptoms (see pages 19-20).
Pimozide
Pimozide (Orap) was approved in this country for treatment of TS in 1984, and is now in fairly common use. Pimozide is a diphenylbutylpiperidine, chemically distinctive from haloperidol or phenothiazines, with potent dopamine blocking properties. Its side effects are similar to haloperidol, but may be less severe and appear in fewer patients. In general, it is better tolerated than haloperidol and probably is of equal efficacy. Concern about cardiotoxicity was raised by initial reports of EKG abnormalities (U waves, inverted T waves, and Q-T prolongation) in early studies. Further investigations with larger numbers of patients have not justified those concerns. Nevertheless, routine EKG studies before and periodically during treatment are still advised.
Treatment with pimozide is initiated at 1 mg/day, and dosage is gradually increased, on clinical indications, to a maximum of 6-10 mg/day for children and 20 mg/day for adults. (The Physicians' Desk Reference indicates that doses greater than 0.2 mg/kg or 10 mg/day are not recommended.) Because of its long half-life (55 hours), a single daily dosage may be feasible. Major side effects are similar to haloperidol and, as with haloperidol, tardive dyskinesia is a possibility.
Other Neuroleptics
Phenothiazines, particularly fluphenazine, may be effective alternatives to haloperidol and pimozide. Fluphenazine's side effects are potentially the same as those associated with haloperidol, but, as with pimozide, some patients tolerate them better. The recommended dose range is similar to haloperidol and the same principles (lowest possible starting dose and gradual increases) are applicable. Other neuroleptics that have been reported to be effective in a few patients include thiothixene, chlorpromazine, and trifluoperazine.
Clonidine
Clonidine (Cataprese) is an imidazoline compound with alpha-adrenergic agonist activity. In low doses it "down-regulates" alpha-adrenergic neurons in the locus ceruleus, decreasing the release of central norepinephrine. Since 1979 it has been considered to be of benefit for the treatment of TS although the response rate is lower than that of either haloperidol or pimozide. In general it is of advantage because of the low incidence of side effects associated with its use. Perhaps of greatest importance is that it does not have the potential of causing tardive dyskinesia. Clonidine has been approved by the FDA only for use in hypertension, but clinicians can prescribe it for TS without special government approval as long as they understand its indications and share the basis for their decision with the family and child.
In addition to reducing the simple motor and phonic symptoms in TS, clonidine seems especially useful in improving attentional problems and ameliorating complex motor and phonic symptoms.
In general, clonidine is started at low doses of 0.05 mg/day and slowly titrated over several weeks to 0.15-0.30 mg/day. Since clonidine has a 6 hour half-life it is important that patients take small doses 3 to 4 times each day. (An alternative to multiple doses is the transdermal patch that needs to be changed only once a week.) Doses of 0.4 mg daily are not infrequent, but doses above 0.5 to 0.6 mg/day are more likely to lead to side effects. When the medication is working effectively, patients may experience the need for their next dose by sensing an increasing anxiety, frequency of symptoms, or irritability. Unlike haloperidol, which may lead to clear improvement within a few days, clonidine tends to have a slower onset of action. When larger doses are used earlier, improvement may occur sooner, but there may be more sedation. With slower titration to therapeutic levels, clonidine may take three weeks or longer to show a beneficial effect.
The patient may experience a reduction in tension, a feeling of being calm, or a sense of having a "long fuse" before tics are reduced. A gradual decrease in complex motor tics and compulsions also may precede clear improvement in simple tics. In the most successful cases, attentional, behavioral, and complex phenomena seem more responsive than the simpler tics. Evaluation of the medication's effectiveness may not be possible before three to four months. When there is a positive response, improvement may progressively appear over many months and up to a year or more later. Patients gain confidence in themselves, adjust better to school, feel less irritable, and have fewer tic symptoms. Those therapeutic benefits reinforce each other.
The major side effect of clonidine is sedation, which appears early in the course of treatment and especially if the dose is increased quickly, but which tends to abate after several weeks. A few patients have dry mouth, although it is experienced less often by children than by adults. There are occasional reports that patients feel that things are "too bright," perhaps because of the impairment of pupillary contraction. At high doses, there may be hypotension and dizziness, particularly if clonidine is given at high doses quite early or if it is increased to over 0.4 or 0.5 mg/day. At lower doses, blood pressure is not clinically affected, although a fall of several mm mercury in diastolic and systolic pressure can be detected. Slight prolongation of the PR interval on the electrocardiogram has been noted, but this has not been considered to be of significance. Increased irritability, nightmares, and insomnia have also been reported.
When clonidine is withdrawn, it should be tapered gradually (see page 20).
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| lucci
Forum Senior
Topics: 35
Posts: 52
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Thank you very much for all your answers!
Good reference, bikerdoc.
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| goodyear
Forum Guru
Topics: 16
Posts: 409
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wow thanks...
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