Drug Induced Movement Disorders
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Drug Induced Movement Disorders Dr Kigocha Okeng’o Neurophysician Muhimbili National Hospital Dar Es Salaam Tanzania Introduction 44% of patients in Ethiopia, 5.67% in India • Therapeutic and illicit drugs can cause movement disorders • Antipsychotics and antiemetics most commonly implicated • Severity ranges from mild to severe and life-threatening • Early recognition of a drug-induced movement disorder is essential to allow for prompt intervention • Tadesse Misgana,1 Niguse Yigzaw,2 Getachew Asfaw3Drug-Induced Movement Disorders and Its Associated Factors Among Patients Attending Treatment at Public Hospitals in Eastern Ethiopia https://doi.org/10.2147/NDT.S261272, • Nimisha et al Prevalence and pattern of antipsychotic induced movement disorders in a tertiary care teaching hospital in India - a cross-sectional study, Int J Psychiatry Clin Pract, 2018 Jun;22(2):101-108. INTRODUCTION… • Symptomatology is often indistinguishable from that of idiopathic movement disorders • resemble that of several other medical conditions • Careful drug history, recognition of a DIMD may be relatively straightforward • As with idiopathic movement disorders, anxiety and stress will also exacerbate symptoms associated with DIMDs • Patients may develop mixed DIMDs ( more than one type of DIMD) Jack J. Chen, Drug-Induced Movement Disorders: A Primer US Pharm. 32(11)HS16-HS32 Drug induced movement disorders Movement disorder Implicated drugs Akathisia Dopamine receptor blocking drugs Selective serotonin reuptake inhibitors Antiepileptics Tremor Selective serotonin reuptake inhibitors Lithium Tricyclic antidepressants Antiepileptics (e.g. valproate) Bronchodilators Amiodarone Immunosuppressive drugs (tacrolimus, ciclosporin) Serotonin syndrome (usually due to overdose or Selective serotonin reuptake inhibitors combinations of serotoninergic drugs) Serotonin noradrenaline reuptake inhibitors Tricyclic antidepressants Monoamine oxidase inhibitors Lithium Linezolid Opioids (pethidine, tramadol, propentadol) Antiepileptics (valproate, lamotrigine) St John’s wort Drug induced movement disorders Acute dystonic reaction Dopamine receptor blocking drugs (e.g. antipsychotics, metoclopramide) Selective serotonin reuptake inhibitors Parkinsonism Dopamine receptor blocking drugs (e.g. antipsychotics) Calcium channel antagonists (e.g. flunarizine, cinnarizine) Antiepileptics (e.g. phenytoin, valproate, levetiracetam) Antidepressants (e.g. selective serotonin reuptake inhibitors, monoamine oxidase inhibitors) Lithium Chemotherapeutic drugs (e.g. cystosine arabinoside, cyclophosphamide, vincristine, adriamycin, doxorubicin, paclitaxel, etoposide) Immunosuppressive drugs (e.g. ciclosporin, tacrolimus) Toxins (e.g. 1-methyl-4-phenyl-1,2,3,6- tetrahydropyridine (MPTP), organophosphate pesticides, manganese, methanol, cyanide, carbon monoxide and carbon disulphide) CLASSIFICATION OF DIMD • Acute DIMD- Occur within minutes to days of drug ingestion – Neuroleptic malignant syndrome – Serotonin syndrome – Acute dystonia – Acute akathisia & acute myoclonus - parkinsonism-hyperpyrexia disorder • Chronic reversible DIMD: occur within days to weeks of drug ingestion – Tremor – Myoclonus • Chronic potentially irreversible DIMD – Tardive syndromes Akathisia • Common, under-recognised, drug-induced movement disorder that can occur as an acute, subacute or tardive reaction • Reportedly 39% in clozapine-treated patients, 45% with first generation antipsychotics • A sense of internal restlessness, irritability & tension without necessarily manifesting with physical signs • unlike restless legs syndrome which is typically more severe and worse at night • predominantly affects the lower extremities from the hips to the ankles, • predilection for the lower extremities distinguishes akathisia from other antipsychotic-induced syndromes Sahoo S., Ameen S. Acute nocturnal akathisia induced by clozapine. J. Clin. Psychopharmacol. 2007;27(2):205. Akathisia • Occur either after starting a dopamine receptor blocker, dose escalation, or when switching to an alternative drug • Improves following cessation of the offending drug • Anticholinergics, beta blockers, benzodiazepines, amantadine, mirtazapine and clonidine have also been used with varying efficacy and with minimal evidence Akathisia • Pathophysiology: • imbalance between dopaminergic and serotonergic/noradrenergic neurotransmitter systems • overstimulation of the locus ceruleus leading to a mismatch between the core and the shell of the nucleus accumbens • neuroinflammation, damage to the blood brain barrier, and/or impaired neurogenesis Drug-induced tremor • Typically postural, kinetic, or both • Symmetrical and occurs acutely following drug ingestion or dose escalation • Exceptions include tremor secondary to valproate, which can appear at therapeutic or during stable treatment, or, rarely, tardive tremor • Can occur secondary to many drugs, including SSRIs, lithium, tricyclic antidepressants, antiepileptics (particularly valproate), bronchodilators, amiodarone and immunosuppressives. • Parkinson’s disease, essential tremor or hyperthyroidism, needs to be excluded Drug-induced tremor • Exact mechanism of DIT is unknown for most medications that cause tremor • In most cases physiological tremor is influenced by these medications • Epinephrine- lead to tremor by peripheral mechanisms in the muscle (β-adrenergic agonists) • Other drugs can cause tremor by blockade of dopamine receptors in the basal ganglia (dopamine-blocking agents) • amiodarone causes hyperthyroidism- tremors Management Of Drug-induced tremor • Altering the dose, stopping the offending drug • Switching to an alternative drug • Should the offending drug need to be continued • discuss the risks of the adverse effects versus the benefits of continuing to ensure the patient is informed • If the drug is continued, drugs typically used for essential tremor (for example, propranolol) can occasionally be beneficial Serotonin syndrome Serotonin Syndrome The most misdiagnosed MD emergency • Clinical features: – EPS (tremor and rigidity) – Dysautonomia – Altered consciousness • Boyer EW & Shannon M, 2005 Serotonin Syndrome • Associated features – Myoclonus – Hyperreflexia – Seizures • Much quicker than NMS -hours rather than days Serotonin Syndrome Serotonin Syndrome • Implies exposure to a single serotonergic agent or more • commonly, exposure to two or more drugs w/ serotonergic properties NOT JUST ANTIDEPRESSANTS • Triptans • Metoclopramide • Valproate • Lithium • Cocaine • Amphetamine • Tramadol • Phentanyl TREATMENT All pts (even mild forms): • Removal of causal agent • Control of agitation w/ benzodiazepines • Supportive care w/ cardiovascular stabilisation – Moderately ill: • 5-HT2A (serotonin receptor) antagonists (Tabs. cyproheptadine 12 mg stat then 2mg every 2 hours, chlorpromazine 50-100 mg iv) till sx are controlled – Severely ill (body temp. ≥ 41.1 ºC): • Orotracheal intubation and immediate paralysis Serotonin syndrome Acute dystonic reactions • Commonly occur in younger patients soon after taking dopamine receptor blocking drugs, including antiemetics (e.g. metoclopramide or prochlorperazine), antipsychotics • Young males more susceptible to dystonic reactions • Acute sustained dystonic spasm of craniocervical muscles is typical, • oculogyric crises, truncal spasm causing opisthotonus, or limb dystonia can also occur • Acute laryngeal dystonia can be life-threatening due to airway obstruction and requires emergency medical care Acute dystonic reactions • Usually within 24h after starting/increasing/switching the drug, but 50% within 48h and 90% within 5 days • Self-limited, but stressing and life threatening if airway compromised • Kipps et al, 2005 • Mazurek, 1991,92,96 Medications likely to induce acute dystonia • Anticonvulsivants • Antipsychotics -carbamazepine -Typical and atypical -gabapentine • Antibiotics • Antiemetics -erythromycin -foscarnet -metoclopramide, • Antihistamines (H2) -ranitidine -prochlorperazine -cetirizine • Antidepressants • Recreational -cocaine -SSRIs & SNRIs Acute dystonic reactions • Older individuals carry less risk for the development of dystonia due to diminished numbers of D2 receptors with aging • Agents that balance dopamine blockade with muscarinic M1 receptor blockade, like atypical antipsychotics, are less likely to elicit dystonic reactions Pathophysiology of Acute dystonic reactions • Occasionally dose related, reactions are more often idiosyncratic and unpredictable • Arise from a drug-induced: • alteration of dopaminergic-cholinergic balance in the nigrostriatum (i.e, basal ganglia) • nigrostriatal dopamine D2 receptor blockade leading to excess of striatal cholinergic output • High-potency D2 receptor antagonists are most likely to produce an acute dystonic reaction Management Of Acute dystonic reactions • Acute episode • Prophylaxis after acute episode - Parenteral anticholinergics - Oral anticholinergics for 4-7 days - Benztropine 1-2 mg IV or IM, and then tapper slowly repeated in 20‘ - Avoid future exposure for - Biperiden IM or scopolamine precipitating drug - Parental diazepam (2-5 mg) or • Primary prophylaxis lorazepam (1-2 mg) - Controversial - Resolves within 15-20 minutes - High risk patient: 1 week of anticholinergic - Prolonged use: discouraged Parkinsonism-hyperpyrexia disorder • Known as akinetic crisis • rare but potentially fatal complication of Parkinson’s disease(PD) • syndrome of significantly worsening parkinsonism (with or without encephalopathy), hyperpyrexia, autonomic instability and elevated