A N T O N I O A V E R S A C U R R I C U L U M V I T A E INFORMAZIONI PERSONALI ANTONIO AVERSA 03.11.1964 Consulente Dipartimento Medicina Sperimentale, Sapienza Università di Roma 06/45421411 335/6642900 [email protected] ANTONIO AVERSA ISTRUZIONE E FORMAZIONE Laurea in Medicina e Chirurgia 1990 Università “Sapienza”, Roma - Abilitazione al a p
Doi:10.1383/medc.18.104.22.168169Features of tic disorders
Psychiatric effects of drugs
• Repetitive, purposeless, stereotyped movements (motor or for other disorders
• Intensity increased by excitement, anxiety or fatigue • Sufferers attempt to disguise the movements by incorporating • Movements can be suppressed for minutes to hours, at the expense of increasing anxiety and compulsion to perform them Mannerisms/habit disorders
• Tic disorder in ‘normal’ individuals Transient tic disorder
Neuropsychiatric effects account for up to 30% of adverse drug • Motor or vocal tics lasting 4 weeks to 12 months reactions (ADRs). Many of these ADRs, ranging from anxiety Chronic tic disorder
states to delirium, are caused by therapeutically administered non- • Motor or vocal tics lasting > 12 months psychiatric drugs, and many drugs can cause a variety of psychi- Tourette’s syndrome
atric effects. The incidence of such reactions is not always known because the information usually depends on selected patient groups or individual reports. In general, psychiatric ADRs are more common in elderly or ill patients and in those with a psychiatric his- • Cause significant distress or functional impairment tory or family history. Other factors include metabolic status, drug interactions and personality. The ADRs are usually dose-related, Coprolalia (involuntary uttering of obscenities) but can occur at therapeutic doses and plasma concentrations in Copropraxia (involuntary obscene gestures) previously normal individuals with no innate vulnerability, and can also occur on drug withdrawal. The mechanisms are often Echopraxia (imitation of others’ actions) complex and vary between drugs and clinical situations. Manage- Pallilalia (repetition of the last word/phrase spoken) ment may be simple if the cause is known, but patients who are taking several different drugs may need careful assessment.
A full discussion of all of the drugs that can cause psychiatric effects is beyond the scope of this contribution; a selection of the more common ADRs is given here.
Management: dopaminergic antagonists such as haloperidol and
tetrabenazine are used to treat the chorea. Clonazepam may help
Parkinson’s disease and parkinsonism
sleep disorders. Counselling and antidepressants should be tried in those with mood disorders, and carbamazepine or valproate Dopaminergic and antimuscarinic agents – dopaminergic
drugs can cause depression, agitation, paranoid psychosis, mania, hypomania and excessive daytime sleepiness. The incidence of psychiatric problems was 20% in one series of 908 patients treated with levodopa for Parkinson’s disease. Delirious states occurring REFERENCES
with bromocriptine can be serious, involving confusion, aggres- 1 Lambert M V, Schmitz E B, Ring H A et al. Neuropsychiatric aspects of
siveness, florid delusions and hallucinations, which can last for epilepsy. In: Schiffer R B, Rao S M, Fogel B S, eds. Neuropsychiatry. weeks after discontinuation of the drug. Similar effects have been 2nd ed. Philadelphia: Lippincott, Williams & Wilkins, 2003: reported with apomorphine, lysuride, pergolide and selegeline. These effects are usually dose-related but are exacerbated by 2 Peterson B S. Neuroimaging studies of Tourette syndrome: a decade
antimuscarinic agents, which are often used concomitantly in of progress. Adv neurol 2001; 85: 179–96.
Parkinson’s disease and can also cause delirium. In addition, they 3 Paulsen J S, Ready R E, Hamilton J M et al. Neuropsychiatric aspects
can cause confusion and dementia, and may contribute to cogni- of Huntington’s disease. J Neurol Neurosurg Psychiatryy 2001; 71:
tive impairment in patients with Parkinson’s disease.
Managementt of psychiatric symptoms in parkinsonism in-
volves withdrawal or reduction of dose of the offending drug. The Haddad M S, Cummings J L. Huntington’s disease. Psychiatr Clin North psychiatric effects of dopaminergic agents may be dose-limiting, Am 1997; 20: 791–807.
particularly in elderly patients and those with post-encephalitic (A good review of neurological and pathological aspects.) disease, and the appearance of symptoms may be delayed. Delirium Lambert M V, Robertson M M. Depression in epilepsy: etiology, caused by anticholinergic drugs or amantadine can be reversed phenomenology and treatment. Epilepsia 1999; 40: (Suppl. 10):
rapidly with intravenous physostigmine. Benzodiazepine tranquil- Robertson M M. Tourette syndrome, associated conditions and the complexities of treatment. Brain 2000; 123: 425–62.
C Heather Ashton is Emeritus Professor of Clinical Psychopharmacology
(An excellent review of the neurology and psychiatric aspects.) at the University of Newcastle upon Tyne, UK. 2004 The Medicine Publishing Company Ltd Psychiatric effects of some drugs for other disorders
Disorders and drugs
Parkinson’s disease, parkinsonism
• Dopaminergic agents (e.g. levodopa, bromocriptine, Delirium, depression, agitation, paranoid psychosis, mania, amantadine, apomorphine, lisuride, selegiline) • Antimuscarinic agents (benzatropine, biperiden, orphenadrine, Exacerbate effects of dopaminergic agents; confusion and dementia Chronic spastic conditions
• Skeletal muscle relaxants (baclofen, dantrolene, tizanidine) Anxiety, agitation, insomnia, nightmares, euphoria, confusion, Cardiovascular disorders
• Digitalis preparations (digoxin, digitoxin) Delirium, depression, hallucinations, psychosis (causing potassium loss) (thiazides, frusemide, May exacerbate toxic effects of digitalis preparations • β-adrenoceptor antagonists (e.g. propranolol, atenolol, Sleep disturbance, nightmares, hypnogogic or hypnocampic • Anti-arrhythmic agents (e.g. lignocaine, procainamide, • Calcium channel blockers (e.g. nifedipine, diltiazem) Confusion, depression, nervousness, sleep disturbance Endocrine disorders
• Glucocorticoids (e.g. prednisolone, betamethasone, Euphoria, mania, depression, psychosis, violent behaviour • Oestrogens and progestogens (contraceptives, hormone Depression, premenstrual tension-like symptoms, changes in libido replacement therapy, treatment of menstrual abnormalities) • Male sex hormones and anabolic steroids (e.g. testosterone, Depression, anxiety, changes in libido; mania, psychosis, aggression and withdrawal symptoms with high doses of anabolic steroids Pain syndromes
• Opioids (e.g. morphine, diamorphine, pethidine, Dysphoria, depression, psychosis (particularly mixed agonists/ dihydrocodeine, tramadol, pentazocine, nalbuphine, anti-inflammatory drugs (e.g. ibuprofen, Nervousness, depression, drowsiness, insomnia; may aggravate diclofenac, pirioxicam, celecoxib, rofecoxib) depression and other psychiatric disorders Gastrointestinal disorders
• H -receptor antagonists and proton pump inhibitors Bacterial, parasitic and viral infections
• Antibiotics (e.g. chloramphenicol, streptomycin and related Delirium, psychosis; sleep disorders, hallucinations, convulsions with drugs, cephalosporins, isoniazid, cycloserine, quinolones) • Antimalarials (mefloquine, chloroquine, mepacrine, quinine) Anxiety, panic, insomnia, nightmares, dysphoria, mania, psychosis, • Antivirals (aciclovir and related drugs, zidovudine and related Drowsiness, hallucinations, depression, insomnia, anxiety lizers may be helpful, but antipsychotic drugs with antimuscarinic UK Committee on Safety of Medicines has warned that serious side-effects can occur on abrupt withdrawal of baclofen, which Other medical conditions – bromocriptine has caused schizo-
should be discontinued by gradual dose reduction over several phreniform or manic reactions when used for post-partum sup- pression of lactation and in the treatment of pituitary tumours. Use of mydriatic eye drops containing antimuscarinics has been Cardiovascular disorders
associated with delirium, hallucinations and amnesia.
Skeletal muscle relaxants such as baclofen used for chronic Digitalis
preparations can cause delirium, depression, halluci-
spastic conditions often cause sedation, and sometimes cause nations and psychosis. The effects are usually dose-dependent and anxiety and agitation with insomnia. Other reported symptoms the likelihood of psychiatric toxicity increases progressively with include euphoria, nightmares, confusion and hallucinations. The plasma digoxin concentration from 1.5–3 µg/litre. ADRs can also 2004 The Medicine Publishing Company Ltd occur at normal doses, particularly in combination with diuretics incidence of dysphoria, including depression, is much higher causing potassium loss. The mechanisms are probably multiple (10%) with mixed agonists/antagonists such as pentazocine and include electrolyte disturbance and cerebral hypoxia result- and nalbuphine. Morphine and other opioids occasionally cause ing from cardiac failure. Management comprises discontinuation paranoid thinking and hallucinations, but psychotic reactions are of the drug and correction of any hypokalaemia. Digoxin-specific more common with pentazocine and the non-opioid analgesic antibody fragments are available for life-threatening toxicity.
nefopam. Dependence is seldom a problem when the drugs are β-adrenoceptor antagonists – the most common psychiatric
used clinically for pain relief. However, withdrawal reactions may effect of these drugs is sleep disturbance, including drowsiness, occur, and discontinuation should be gradual and combined with insomnia, vivid dreams, nightmares, and hypnogogic or hypno- campic hallucinations. These occur mostly with the lipophilic Non-steroidal anti-inflammatory drugs – all of these agents,
agents (e.g. propranolol), with which the incidence of drowsiness including COX-2 inhibitors, can cause nervousness, depression, and fatigue is about 4%; vivid dreams and hallucinations at onset drowsiness or insomnia. The risk appears to be greatest with indo- of sleep or waking are more common. The effects are generally methacin, which may aggravate depression and other psychiatric dose-related, but have been reported in individuals taking pro- disorders, epilepsy and Parkinson’s disease.
pranolol at a dose of only 30 mg/day. Similar symptoms occa-sionally occur with water-soluble preparations such as atenolol. Gastrointestinal disorders
Both lipophilic and water-soluble agents can cause depression (incidence 1–5%) and both occasionally cause delirium.
Both H -receptor antagonists and proton pump inhibitors can cause Other cardiovascular drugs – psychotic reactions have been
depression, somnolence or insomnia, agitation and confusion with reported with several anti-arrhythmic agents and calcium channel hallucinations, particularly in elderly or severely ill patients.
blockers. Angiotensin-converting enzyme inhibitors may cause confusion, depression and nervousness.
Bacterial, parasitic and viral infections
Antibiotics seldom cause psychiatric side-effects, but delirium
and paranoid–hallucinatory psychosis have been reported with Glucocorticoids – long-term use of systemic glucocorticoids
chloramphenicol, streptomycin and related drugs, cephalosporins can cause a spectrum of psychiatric reactions in up to 5% of pa- and some antituberculous drugs. Quinolones can cause sleep tients; these range from euphoria, mania and suicidal depression disorders, restlessness, depression, confusion and hallucinations, to schizophreniform paranoid psychosis with violent behaviour. and may induce convulsions in patients with or without a history Schizophrenia and epilepsy may be aggravated, and depressive reactions are more likely in patients with a positive family history. Antimalarials – of these agents, mefloquine has the greatest
The effects are usually dose-related and can occur in patients with propensity to cause neuropsychiatric effects. The incidence of no psychiatric history. Long-term use leads to drug dependence, severe reactions is only about 0.01%, but milder reactions are and psychiatric reactions of all types can occur on withdrawal. The more common. The most common are anxiety, panic, insomnia, therapeutic glucocorticoid dose varies widely between conditions nightmares and dysphoria, which usually appear within 3 weeks and individual patients, but to minimize side-effects the main- of starting prophylactic dosing. Severe reactions include mania tenance dose should be kept as low as possible and withdrawal and paranoid–hallucinatory psychoses, which may also occur with chloroquine and mepacrine. Higher doses used for treatment of Oestrogens and progestogens carry a slight risk of depression,
malaria may precipitate delirium. Mefloquine is contraindicated particularly in women taking high-dose oestrogen. They may also in patients with a history of neuropsychiatric disorder.
cause a premenstrual-like syndrome with sodium and fluid reten- Antivirals – aciclovir and related drugs can cause drowsiness
tion, and can cause headaches and changes in libido.
and hallucinations; protease inhibitors are associated with mood Male sex hormones and anabolic steroids – testosterone can
disorders including depression and sleep disturbances. Zidovudine cause depression, anxiety, asthenia and changes in libido. Anabolic and related drugs may cause general malaise.
steroids can cause euphoria or depression, particularly at higher Interferons – interferon-α and interferon-β may induce depression
doses. They are sometimes abused in large doses by body-builders and suicidal behaviour. Interferon-β is contraindicated in patients and athletes, and can lead to dependence. Psychiatric effects are with a history of severe depression or suicidal ideation. common in this setting and may occur both during use and on withdrawal. In some studies, the incidence of mania and hypo-mania has been reported to be more than 20%, and psychosis and FURTHER READING
hallucinations more than 10%. Irritability, aggression and violence Bazire S. Psychotropic drug directory. Dinton: Allen, 2001.
are also common. Depression, with risk of suicide, may be severe (Contains a useful section on drug-induced psychiatric disorders.) on withdrawal, and 50–80% of abusers report milder symptoms British National Formulary. London: British Medical Association, of fatigue, restlessness, insomnia, reduced libido and craving.
Royal Pharmaceutical Society of Great Britain.
Davies D M, Ferner R E, de Glanville H. Textbook of adverse drug reactions. 5th ed. London: Chapman & Hall, 1998.
(Includes a chapter on drug-induced psychiatric disorders.) Opioids – pure opioid agonists such as morphine may cause
Dukes M N G, Aronson J K. Meyler’s side effects of drugs. 14th ed. dysphoria in 1–2% of patients treated for chronic pain, but the 2004 The Medicine Publishing Company Ltd
Ackumulationeller bioackumulation är anrikning av exempelvis ett gift i växter och djur. Det är ämnen som bryts ner långsamt eller inte alls förs vidare i näringskedjan och koncentreras hos djuren i kedjans slut. De utsöndras inte ur kroppen utan lagras i vävnader i t ex njurar eller fettvävnad. Kadmium, kvicksilver, DDT och PCB är exempel på ämnen som ackumuleras. Agenda 21är ett a