TD Symptoms

Combined risperidone and electroconvulsive therapy (ECT) produced a remarkable improvement in one patient s refractory depression, but it also caused a return of prior TD symptoms (106). When clozapine was added to the ECT-risperidone regimen and risperidone was tapered gradually, the patient s TD signs and symptoms remitted, and she responded well to combined ECT and clozapine. 

Furthermore, at the times they were being evaluated, the patients continued to take the olanzapine, which, like all neuroleptics, suppresses the appearance of TD symptoms while at the same time causing or worsening the underlying disorder (see subsequent section). Therefore, the only way to determine an accurate rate of TD is to withdraw the patients from the offending drug before the final evaluation. In this study, the actual rate of TD would have been much higher than 3% per year if the patients had been withdrawn from the olanzapine before the final TD evaluation. 

Fann et al., 1980 Klawans, 1973 and chapter 5 in this volume). This supersensitivity of the dopamine receptors becomes most obvious when the drug is reduced or eliminated, terminating the blockade. The over-active, unblocked receptors produce the TD symptoms. Undoubtedly, a great deal more must be learned about the neuropathology of both these drug-induced diseases, which probably involve multiple neurotransmitter system abnormalities. However, if health care providers were to stop prescribing these drugs to patients, the problem would virtually disappear. 

A clinical study of hospitalized drug-treated patients found many suffering from mental deterioration typical of a chronic organic brain syndrome that the researchers labeled dysmentia (Wilson et ah, 1983). Tardive dysmentia consists of unstable mood, loud speech, and [inappropriately close] approach to the examiner. It is probably a variant of hypomanic dementia.1 The mental abnormalities in the study by Wilson et al. (1983) correlated positively with TD symptoms measured on the Abnormal Involuntary Movement Scale. In addition, length of neuroleptic treatment correlated with three measures of dementia unstable mood, loud speech, and euphoria. The authors stated, It is our hypothesis that certain of the behavioral changes observed in schizophrenic patients over time represent a behavioral equivalent of tardive dyskinesia, which we will call tardive dysmentia (p. 188). The tendency in the literature, perhaps in search of a euphemism, has been to use the term tardive dysmentia even when a full-blown dementing syndrome is described. 

In addition to Wilson et al. (1983), several other studies reported an association between TD symptoms and generalized mental dysfunction (Baribeau et al., 1993 DeWolfe et al., 1988 Itil et al., 1981 Spohn et al., 1993 Struve et al., 1983 Waddington et al., 1986a b Wolf et al., 1982 many reviewed in Breggin, 1993). After eliminating schizophrenia as a causative factor, Waddington and Youssef (1988) also found increased cognitive deficits in neuroleptic-treated bipolar patients with TD in comparison to those without the disorder. 

Symptom Rating Scale (ESRS). Akathisia is commonly monitored by the Barnes Akathisia Scale (BAS). The emergence of dyskinesias (writhing or involuntary movements) could represent the emergence of TD. Monitor for TD at least annually, and if FGAs are used patients should be evaluated at each visit. The most commonly used instrument to measure these symptoms is the Abnormal Involuntary Movement Scale (AIMS). 

Chung T, Martin CS, Armstrong TD and Labouvie EW (2002). Prevalence of DSM-IY alcohol diagnoses and symptoms in adolescent community and clinical samples. Journal of American Acadamy of Child and Adolescent Psychiatry, 41(5), 546-554. 

Dosage reduction or discontinuation may have significant effect on outcome, with a complete disappearance of symptoms in some patients (especially if implemented early in the course of TD). 

Risk factors for TD include duration of antipsychotic therapy, higher dose, possibly cumulative dose, increasing age, occurrence of acute extrapyrami-dal symptoms, poor antipsychotic response, diagnosis of organic mental disorder, diabetes mellitus, mood disorders, and possibly female gender. 

Many DA receptor antagonists (neuroleptics) for treating psychoses (for example, schizophrenia) have become efficient medicines. However, most of them induce severe extrapyramidal side-effects (EPS) akin to parkinsonian symptoms and also, more seriously, they induce tardive dyskinesias (TD). There is a need for improvements in the neuroleptics in the clinic. The substituted benzamides are D2 antagonists, some of which display a high degree of limbic selectivity. Such a regional selectivity has been suggested to be beneficial from the side-effects point of view [11,12]. 

Enterotoxigenic E. coli (ETEC) is the main cause of TD in Latin America, whereas in Asia it is reported in only 15% of cases. Enteroinvasive E. coli (EIEC) strains are recorded with even less frequency. ETEC is isolated in 0 to 5% of cases. Symptoms of poisoning develop after 16 hours from consumption of contaminated water, salads, cheeses, or meats. The outgrowth of ETEC rods takes place in a patient s gastrointestinal tract, where they produce thermostable and thermolabile toxins that imitate Vibrio cholerae infections. Stimulation of intestinal guanylcyclase and interruption of ion transport leads to watery stools, which do not require medical treatment or only need simple replacement of fluids and salts by means of multielectrolyte solutions. If a co-infection with EIEC strains occurs, the symptoms of enteritis will develop, with the presence of leukocytes, erythrocytes, and mucous in stools due to a cytotoxic influence of bacteria (Butterton and Claderwood, 2001). 

EPS = extrapyramidal symptoms OH = orthostatic hypotension TD = tardive dyskinesia. These doses represent usually effective doses but individual patients may respond to lower or higher doses. Should be used rarely due to risk of bone marrow depression. 

Of particular importance in tfie geriatric patient Confusion, drowsiness, extrapyrami-dal symptoms (parkinsonism, tremor), tardive dyskinesia (TD), restlessness, weakness, diarrhea... 

Treatment of the comorbid patient presents a number of challenges (Fig. 39.2). The phenotype of OCD and Tourette s disorder (TD) is encountered frequently as there is a bidirectional overlap between the two conditions. In a review of 11 clinical studies, TD was found in an average of 21% of juvenile OCD subjects (Geller et ah, 1998). These subjects are more often male with an earlier age at onset and positive family history of OCD and tics. Kurlan et al. (1993) suggested that obsessional symptoms might respond less well to the SSRIs in these subjects. 

Because clozapine may block specific DA receptors, its antipsychotic activity could be consistent with an antidopaminergic mechanism of action. Conversely, clozapine does not typically induce extrapyramidal symptoms, which are presumably subserved by the A-9 system. Thus, while clozapine is known to block striatal DA receptors, in positron emission tomography (PET) studies, resolution is not sufficient to clarify effects on other tracts. Furthermore, low doses of metoclopramide, which significantly decrease the number of DA neurons spontaneously active in A-9, do not have antipsychotic effects (except at high doses) but can induce tardive dyskinesia (TD), as well as acute extrapyramidal side effects (EPS). 

All clinically effective antipsychotics block DA receptor activity. Further, stimulation of this neurotransmitter can induce psychotic symptoms de novo or exacerbate an existing psychotic disorder. Atypical agents have differential impacts on other systems (e.g., 5-HT) in comparison with the earlier neuroleptic agents. They also selectively target specific DA tracts that may mediate the pathological condition, while sparing those tracts that mediate the unwanted adverse effects (e.g., EPS, TD). 

Antipsychotics are a chemically diverse group of drugs having in common the ability to ameliorate psychotic symptoms. Unfortunately, a significant percentage of patients fail to respond adequately or may develop adverse effects such as acute EPS, various tardive syndromes (e.g., TD, dystonia, etc.), and, less commonly, even more serious adverse events such as NMS and agranulocytosis. 

In this context, Lilly (474) reported a meta-analysis of three controlled studies of patients with TD who were treated with olanzapine. These authors found an 11-fold decrease in TD on olanzapine versus haloperidol based on the AIMS scale. There were a few patients who developed TD in the first 6 weeks of olanzapine, but this could have been from previous drug exposure, now not suppressed by the neuroleptic. Interestingly, there were no new cases (0/375) of TD developing in patients on long-term olanzapine treatment, whereas there were three of 83 cases on haloperidol. It is very difficult to arrive at definitive evidence about TD because most patients have received previous neuroleptic therapy and because TD-like symptoms occur spontaneously, providing an alternative explanation. It is clear that it is difficult to prove that olanzapine causes TD but equally difficult to prove that it does not. The 11-fold decreased incidence, however, is strong evidence that at least it produces much less TD. 

Nickel JC, Sander S, Moon TD A meta-analysis of the vascular-related safety profile and efficacy of alpha-adrenergic blockers for symptoms related to benign prostatic hyperplasia. Int J Clin Pract 2008 62 1547. [PMID 18822025]... 

SVT supraventricular tachycardia Sx symptom synd syndrome Sz seizure tab/tabs tablet/tablets tach tachycardia TB tuberculosis TBI traumatic brain injury TCA tricyclic antidepressant (class of drugs commonly used to treat depression, e.g., amitriptyline) TCP transcutaneous pacing TD transdermal TFT thyroid function test TIA transient ischemic attack tid three times a day (Latin ter in die ) tine tincture TMP trimethoprim (type of antibiotic)... 

A 57-year old Caucasian man with inflammatory bowel disease was given prednisolone metasulfobenzoate sodium enemas twice daily and oral mesalazine 800 mg tds for about 5 months, without improvement. He stopped using the prednisolone enemas but continued to take mesalazine. Within 48 hours of stopping prednisolone his symptoms resolved completely. The theoretical possibility of contact allergy was entertained. Patch tests with a standard battery of contact allergens, including tixocortol pivalate and budesonide, were ++ positive with budesonide. At follow up 3 months later he was symptom free. 

To further examine the risk of atypical neuroleptics causing TD in children, Wonodi and a team from the Maryland Psychiatric Research Center (2007) followed up 118 children who had been taking neuroleptics, mostly atypicals, for at least 6 months. As a sign of the irrational overprescription of these drugs, only 19% of the children on antipsychotic drugs had ever displayed psychotic symptoms. 

Masking the Symptoms of TD With Continued Neuroleptic Treatment... 

The symptoms of TD are paradoxically masked or suppressed by the drugs that cause them so that the disease symptoms do not fully appear until the patient has been removed from the treatment. For this reason, in addition to using the smallest possible dose for the shortest possible time, whenever possible, patients should periodically be removed from their neuroleptics, if only for a short period, to determine if they are developing TD. Permanent removal from the neuroleptics is a more difficult matter,... 

The question naturally arises, Do acute EPS increase the risk of TD If acute EPS do predict an increase in future TD, then the emergence of EPS indicates an increased need to terminate the medication. These questions have been debated over the years, but recent research gives the best-informed answer to date. In 2006 a prospective follow-up study of 9,298 patients by the European Schizophrenia Outpatient Health Outcomes (SOHO) Study found a statistically significant correlation between baseline EPS and later TD. According to Tenback et al. (2006), about half of the patients who developed tardive dyskinesia had earlier extrapyra-midal symptoms. They concluded that drug regimens... that increase extrapyramidal symptoms are likely to result in increased risk of tardive dyskinesia. ... 

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