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ADVERSE PSYCHIATRIC REACTIONS TO PRESCRIBED DRUGS

Iatrogenic Psychiatric Disorders (Medication Induced Disease) (Section 1)

Jump to: Section 2 (list modified from McConnell and Duffy, 1994)

Most of the following text is quoted from the Textbook of Adverse Drug Reactions - Davies 1991 Oxford University Press (OUP) Psychiatric disorders section by K. Davison and F. Hassanyeh

"Adverse drug reactions account for a substantial amount of psychiatric morbidity (illness) which is increasing as new and ever more potent drugs are introduced. A survey of adverse drug reactions in general practice revealed that neuropsychiatric reactions accounted for 30 per cent of cases, second only to gastrointestinal reactions (Martys 1979) The Boston Collaborative Drug Surveillance Program (BCDSP 1971) recorded adverse psychiatric reactions in 2.7 per cent of 9000 hospital patients receiving non- psychiatric drugs.

The difficulties attaching to establishing the validity of any alleged drug reaction are greatly magnified for psychiatric reactions. The latter may be delayed in onset, and some reactions may persist for weeks or months after drug withdrawal.

The chapter continues after elaborating on the difficulties.

"Many reports emanate from non-psychiatrists, who tend to equate hallucinations and delusions with ' psychosis' or even 'schizoprenia' and apathy with ' depression' when the correct diagnosis is 'delirium'.

Application of a recognized diagnostic system, such as the International Classification of Diseases (ICD-9) (WHO 1977) or that of the American Psychiatric Association (DSM-111-R) (APA 1987) would help to obviate this difficulty. These problems emphasize importance of national systems of reporting adverse drug reactions.

Predisposing factors to adverse psychiatric reactions

An important variable in the production of adverse psychiatric reactions is personal predisposition. The risk of increased in those with pre-existing impairment of brain function, such as the elderly or brain-damaged, or with past or present psychiatric illness, or a history of alcohol or drug abuse, but those with unblemished psychiatric records are by no means immune. Although a family history of affective disorder (depression or mania) predisposes to the drug precipitation of the same conditions. (Whitlock and Evans 1978), the relationship is less clear - cut for paranoid or schizophreniform psychoses (Davison 1976). These disorders can also appear in those without such predisposition.

Other predisposing factors include extreme youth (Prescott 1979), concurrent physical disease (James 1975), and stressful environments, such as intensive treatment units (Tomlin 1977; Davison 1989a)

Types of Reaction

The vast majority of adverse psychiatric drug reactions are of Type A in that they are dose-dependent or recognizably related to the known pharmacological properties of the drug. Even when a reaction occurs at therapeutic plasma drug levels there is often an interaction of an identifiable drug effect with individual predisposition." END OF QUOTE

The following is quoted from 'Iatrogenic Diseases by D'Arcy and Griffin 1986 (OUP)

If an unexpected psychiatric disturbance arises suddenly in a person of good previous personality, shortly after a drug of any sort has been taken, no matter how harmless it usually is, it is clearly wise to suspect a drug-induced reaction and, if possible, to discontinue or reduce the dose of the suspected medication. It is also good practice to avoid unnecessary polypharmacy, to attempt to treat one psychiatric condition with one drug if possible, and to remember that the use of two drugs from the same group (antidepressant, neuroleptic, minor tranqullizer, etc.) can rarely, if ever, be justified.

Delirium

A very wide range of drugs have been associated with toxic confusional reactions (acute brain syndrome) which are characterized by a fluctuating clouding of consciousness, restlessness, emotional changes (usually fear and perplexity, and paranoid delusions and/ or visual hallucinations in severe cases.)

Detailed descriptions of delirious states were given in the classic paper by Wolfe and Curran (1935) who reviewed 106 cases associated with 27 different precipitating noxious agents. The only drugs involved in these cases were alcohol, barbiturates, bromide, lead and copper. Wider range of drugs can be associated with such reactions, either during administration or in withdrawal." END OF QUOTE

Some Psychiatric Effects: list modified from McConnell and Duffy, 1994

Psychiatric Disorders - Iatrogenic (Doctor Induced) Disease (Section 2)

Drug	Psychiatric Effects
Antihypertensive drugs
Clonidine	depression, mania, agitation
Propanolol	depression, mania, delirium, psychosis
Nifedipine	depression
Captopril	mania, agitation
Antiarrhythmics
Procaninamide	depression, mania, delirium, psychosis
Lignocaine	depression, delirium, psychosis
Disopyramide	delirium, psychosis
Antimicrobial Agents
Penicillins	depression, agitation, visual halucinations
Tetracycline	depression, hallucinations
Cephalosporins	delirium, psychosis
Antimalarials	psychosis, visual hallucinations
Antiparkinson drugs
Anticholinergics	delirium, psychosis, visual hallucinations, dementia
Amantadine	depression, agitation, delirium, psychosis visual hallucinations
Levodopa	depression, mania, anxiety, agitation, psychosis visual hallucinations, delirium, cognitive impairment
Antihistamines
H1 Blockers (diphenhydramine)	delirium
H2 Blockers (cimetidine)	depression, mania, delirium, psychosis, visual hallucinations
Antineoplastic drugs
Interferon	depression, agitation, delirium
Vincristine	depression
C-asparaginase	depression, delirium, psychosis
Endocrine Agents
Corticosteroids	depression, mania, psychosis, delirium
Oral contraceptives	depression
Thyroxine	anxiety, agitation, mania, psychosis, visual hallucinations
Antiepileptic drugs
Barbiturates (phenobarbitone, primidone)	hyperactivity (especially in children), sedation, sexual dysfunction, aggression, learning deficits, cognitive impairmant, depression, personality change Positive effects: anxiolytic/hypnotic (hypnotic, or soporific drugs produce sleep by depressing brain function and often cause hangover effects in the morning)
Benzodiazepines: (clonazepam, diazepam)	aggression, confusion, depression, disinhibition, irritability, cognitive impairment Positive effects: anxiolytic/hypnotic; antimanic (clonazepam)
Carbamazepine	depression, irritability, sexual dysfunction, mania Positive effects: antidepressant, antimanic, treatment of aggression and bipolar disorder
Clobazam	similar side effect profile to other benzodiazepines but may have lower overall incidence of cognitive and behavioural side effects anxiolytic/positive psychotropic effects
Gabapentin	sedation, ataxia, (shaky movements) aggression and hyperactivity (children); Few drug interactions, positive psychotropic effects,
Hydantoins (phenytoin)	sedation, ataxia, dementia, affective disorder, confusion, cognitive impairment, progressive encephalopathy (disease that affects functioning of the brain) Positive effects? antiaggressive, anxiolytic effects
Lamotrigine	may have added toxicity when used with carbamazepine: ataxia, dizziness; positive psychotropic effects
Succinimides (ethosuximide, methsuximide)	Psychosis ("alternating psychosis"- adolescents, young adults) Drowsiness, insomnia, irritability, cognitive effects, personality change, Positive effects: improvement in attention/concentration (likely related to seizure improvement)
Topirimate	sedation, confusion, cognitive dysfunction, asthenia (weakness loss of strength)
Valproate	progressive encephalopathy, dementia, depression, extrapyramidal effects (muscle spasms etc) Positive effects: antimanic, treatment of aggression and bipolar disorder
Vigabatrin	depression and psychosis