Review Article

Psychiatric Morbidity and Other Factors Affecting Treatment Adherence in Pulmonary Tuberculosis Patients

Table 5

Psychiatric disorders in patients receiving TB medications.

Anti-TB drugReported adverse eventFrequency of eventReferences

Isoniazid (INH) or iproniazid (IPH) Toxic psychoses developed while under treatment with isoniazid or iproniazid in combination with other antituberculous drugs5 cases seen at Charity Hospital of Louisiana, at New Orleans[116]

CycloserineShowed some type of neurologic or psychiatric disturbance of varying severity15 out of 30 TB patients
6 showed severe disturbance of function, either manifested by mounting signs of central nervous system instability (grand mal convulsions) or in borderline or outright psychosis.
[117]

Isoniazid and ethambutolPeripheral neuropathy is associated with the use of isoniazid In approximately 17% of patients using doses of 300 mg daily and
lower frequency to the use of ethambutol
[118]

Isoniazid and ethambutolThe optic neuritis manifests with reduced visual field or acuity or color vision
Uncommon during the use of isoniazid and ethambutol/is related to generally at high doses or prolonged use[118]

IsoniazidThe behavioral disorders, changes in the rhythm of sleep, reduced memory, and psychosis have been described for the use of isoniazid. Seizures and coma are described by the excessive intake of isoniazid.Alcoholism, diabetes mellitus, malnutrition, and uremia are all predisposing factors for neurological and psychiatric disorders listed here.[118]

streptomycinThe toxicity acoustic (or vestibular) is a complication related to the use of streptomycin. [118]

IsoniazidMinor adverse effects.
Changes in behavior: headache, insomnia, euphoria, agitation, anxiety, and somnolence can occur in patients receiving isoniazid
[119]

IsoniazidMajor adverse effects:
Psychosis, convulsive seizures, mental confusion, and coma. Attempted suicides have been reported to occur among patients using isoniazid
In patients receiving isoniazid, neurological and psychiatric manifestations are less common, more severe, and often difficult to diagnose. The differential diagnosis with tuberculous meningitis and hepatic encephalopathy should be established. [119]

Isoniazid Out of the five psychotics, three were manic, and two were depressive.
Among the six neurotics, three were depressive and one each of anxiety, obsessive compulsive, and phobic neurosis
11 (five psychotics and six neurotics) out of 732 in patients of the hospital for tuberculosis and chest diseases, symptoms were nondose related[120]

Isoniazid INH-induced psychosis8 cases of INH-induced psychosis out of 4960 hospitalised patients of pulmonary tuberculosis receiving INH[121]

IsoniazidToxic psychosis as a psychiatric side effect during antituberculosis therapy occurred when isoniazid was given in dose ranging from 2.6 milligrams to 4.5 milligrams/kg bodyweight, over a period of eight to thirty six weeks.
Five cases developing psychosis while receiving isoniazid that presented with excessive argumentation, mental depression, euphoria, grandiose ideas, and complex delusions; none of these patients had any previous history of mental illness.[122]

Ethambutol and isoniazidConcomitant occurrence of INH- and EMB-induced psychosis in a single individual A case report: an extremely uncommon event[123]

IsoniazidSymptoms of restlessness, irritability, emotional instability, agitation, apprehension, and fluctuation in behavior after isoniazid therapyA case report
[124]

IsoniazidA case of isoniazid psychosis in a 74-year-old, who developed restlessness, irritability, aimless activity, and incongruous actions 10 days after starting isoniazid therapyA case report
[125]

IsoniazidA case of isoniazid-induced psychosis with disturbed sleep, restlessness, and abnormal behaviorA case report
[126]

EthambutolA 40-year-old man with advanced HIV infection and mycobacterium avium complex infection experienced rapid cognitive decline after commencement of ethambutol, and symptoms fully resolved with cessationA case report
[127]

EthambutolA case of a 51-year-old man with suspected tuberculosis (TB) pleurisy. An anti-TB trial with INH, rifampicin, and EMB was given initially. Dizziness, disorientation, and auditory and visual hallucinations developed after seven days of therapy. When the patient was challenged with EMB, the same psychiatric symptoms recurred but resolved again after discontinuation of
EMB.
A case report
[128]

The neurological manifestations and toxicities of 12 antituberculosis drugs (isoniazid, rifampicin (rifampin), ethambutol, p-aminosalicylic acid, pyrazinamide, streptomycin, kanamycin, ethionamide, cycloserine, capreomycin, viomycin, and thiacetazone) are reviewedIn the Boston Collaborative Drug Surveillance Program performed in 1974.
With rifampicin neurological complications have been observed infrequently, isoniazid is associated with a large number of accidental and intentional poisonings.
More than 35% of adverse effects associated with INH were psychiatric in nature, with an incidence of 1.9%.
Adverse reactions to cycloserine are mainly dose related with neurological and psychiatric syndromes noted in up to 50% of patients.
The highest incidence has been observed with Southwestern American Indians in which this agent was involved in 7% of all suicide attempts and 19% of the suicide deaths.
[129]

IsoniazidIn Peru, severe psychiatric syndromes associated with INH
Occurred in approximately 1.0% of tuberculosis cases between 1991 and 1999[130]

IsoniazidAll case reports describing isoniazid-associated psychosis were reviewed.
Studies were evaluated for the use of isoniazid, symptoms of psychosis, onset of symptoms, and dosage of isoniazid.
The most common psychiatric symptoms associated with INH were delusions, generally presenting after approximately 4 weeks of taking the drug, and among patients of an average age of 35 years (range 17–53). They summarize risk factors as receiving a dose above 5 mg/kg; age 50 years or older; comorbid disease including diabetes mellitus, hepatic insufficiency, alcoholism, and hyperthyroidism; and past psychiatric history.
The incidence of isoniazid-associated psychosis is rare[131]

IsoniazidA patient who developed a psychotic disorder after 4 months of isoniazid prophylaxis for a positive tuberculosis tine test. His symptoms resolved within 2 weeks of discontinuing the isoniazid.[132]

Primary antituberculosis (anti-TB) drugsOut of 1149 patients with established tuberculosis who initially received anti-TB therapy neuropsychiatric manifestations were observed during the initial phase of therapy.In 0.7% of TB patients[133]

EthionamideAdverse reactions like anxiety, depression, and psychosisHas been reported in 1%-2% of patients taking shorter courses of the drug, with higher rates reported with prolonged treatment[134]

EthionamideA patient being treated with streptomycin, isoniazid, pyrazinamide, ethionamide, and prednisolone developed an acute psychotic reaction and died after jumping from a second floor window. It is probable that the reaction was precipitated by the ethionamide.A case report[135]

EthambutolDizziness, disorientation, and auditory and visual hallucinations developed after seven days of therapy. Following discontinuation of anti-TB agents, the psychiatric symptoms subsided. When the patient was challenged with EMB, the same psychiatric symptoms recurred, but resolved again after discontinuation of EMB. EMB may be associated with mania, confusion, and psychosis.A case report[136]

FluoroquinolonesHave been implicated in rare occurrences of psychosis, depression, suicidal ideation, delirium, and nightmares.
CNS toxicity occurs in 1%–4.4% of patients but with serious adverse occurring in less than 0.5% of patients.
A case of a woman who experienced an acute psychosis secondary to ciprofloxacin administration, which resolved on cessation of therapy.
Two cases of organic psychosis, induced by ofloxacin.
8861 patients receiving ciprofloxacin were assessed worldwide, and 138 cases presented with various neurological adverse reactions.
[137]
[138]
[139]
[140]

Ofloxacin or ciprofloxacinIn a retrospective study conducted by the authors, 4189 reports of consultant psychiatric examinations were analyzed. In 29 patients, the suspicion of psychopathological ADR during treatment with ofloxacin or ciprofloxacin was documented. Psychopathological findings included delirious states, paranoid, depressive and manic syndromes, agitation, sleep disturbances, and stupor. In elderly patients, delirious and paranoid syndromes were predominant, whereas affective disturbances occurred more often in younger patients.Reported psychiatric disturbance in 0.7% of 4189 individuals treated with either ofloxacin or ciprofloxacin.[141]

CycloserineSevere psychiatric manifestations—including hallucinations, anxiety, depression, euphoria, behavioral disorders, and suicidal ideation and/or attempts. Psychiatric symptoms appear most likely to present within the first 3 months of treatment.Have been reported to occur in 9.7%–50% of individuals receiving CS. [142]
[143]
[144]
[145]
[146]
[147]
[148]