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General Hospital Psychiatry 34 (2012) 53 – 61

Which psychotropic medications induce hepatotoxicity?

Karim Sedky, M.D., M.Sc. a,⁎, Racha Nazir, M.D. b , Aditya Joshi, M.R.C.Psych., M.D. b ,
Gagandeep Kaur, M.D. c , Steven Lippmann, M.D. c
a
Department of Psychiatry, Drexel University, Philadelphia, PA, USA
b
Department of Psychiatry, Milton S Hershey Medical Center, Hershey, PA, USA
c
Department of Psychiatry, University of Louisville School of Medicine, Louisville, KY, USA
Received 25 May 2011; accepted 18 October 2011

Abstract

Objective: Safe prescribing practices to minimize pharmaceutically induced liver damage or worsening of preexisting conditions require
knowledge about medicines with hepatotoxic potential. This paper reviews psychotropic medications and their effects on the liver.
Methods: A MEDLINE search was performed utilizing the phrase “drug-induced liver injury” with various categories of psychiatric drugs.
Only articles written in English were utilized.
Results: Hepatotoxicity can be acute or chronic in nature. Medication discontinuation is necessary in acute forms, while close monitoring is
required in milder forms of medication-induced chronic liver damage. Nefazodone, pemoline and/or tacrine are the highest offenders.
Carbamazepine and valproate products (e.g., divalproex) can lead to this adverse event and should be avoided in patients with liver disease,
persons with alcohol misuse or those consuming high doses of acetaminophen.
Conclusion: Knowing the risk levels associated with various medicines is important; prescribing multiple drugs with hepatotoxic effects
should be avoided. One should educate patients about early warning signs of liver injury. Always provide clinical and laboratory
monitoring before and during the use of hepatotoxic drugs. Clinical features and laboratory results govern medication prescribing with
ongoing risk-to-benefit ratio assessment during pharmacotherapy.
© 2012 Elsevier Inc. All rights reserved.

Keywords: Psychotropic medicines; Psychiatric drugs; Hepatotoxic drugs; Hepatotoxicity; Medication and liver toxicity; Liver failure; Hepatic dysfunction

1. Introduction tion, and with comorbid medical or liver pathology. Always

consider prescribed and over-the-counter acetaminophen
Drug-induced hepatotoxicity is an important, yet under- dosages and use patterns.
reported, complication [1]. In people taking therapeutic doses Hepatotoxicity is characterized by liver enzyme elevations
of medication, the incidence of drug-induced liver disease is of 1.25 times or more the upper limit of normal and/or the
between 0.001% and 0.1% [2]. Among inpatients on an presence of signs or symptoms signifying such injury,
internal medicine service, the incidence is estimated at 1% including nausea, vomiting, jaundice or lower extremity
[3]. In fact, medication-induced liver failure is a prominent edema. Enzymatic activity above fivefold normal is consid-
cause of liver transplantation [4]. Age, gender, health or ered severe. It is often difficult to determine if a specific drug
nutritional status, and medications taken and their dosages is a definite cause for liver insult. Hepatic damage is
can affect hepatotoxic predispositions. Knowledge about the recognized when injury follows medication initiation, resolves
potential for pharmaceutical toxicity is critical, but especially after discontinuation of that agent and reappears at pharma-
so when utilizing polypharmacy, during alcohol consump- ceutical rechallenge. No other causes of hepatotoxicity should
be present. Yet, most of the published data fail to report many
⁎ Corresponding author. Department of Psychiatry, Drexel University;
of these factors, compounded by it being unethical to
Friends Hospital, 4641 Roosevelt Boulevard, Philadelphia, PA 19124, USA. rechallenge a patient with a drug not well tolerated. The
Tel.: +1 215 831 6400; fax: +1 215 831 4020. definition of acute and chronic hepatic failure varied over the
E-mail address: sedky66@hotmail.com (K. Sedky). years. The most accepted terminology for acute or fulminant
0163-8343/$ – see front matter © 2012 Elsevier Inc. All rights reserved.
doi:10.1016/j.genhosppsych.2011.10.007
54 K. Sedky et al. / General Hospital Psychiatry 34 (2012) 53–61

hepatotoxicity is severe liver damage, with encephalopathy Sertraline has been associated with elevated hepatic
and delirium ensuing within 8 weeks of the onset of the enzymes in 0.8% of treated patients [12]. Seven documented
symptomatology. This usually occurs in an individual with no cases of severe toxicity are associated with this agent [13].
preexisting hepatic disease and results in a high mortality if Fluvoxamine is linked to sporadic instances of hepato-
not appropriately treated. Chronic liver disease is character- toxicity. In a 39-year-old woman, symptomatic enzyme
ized by long-term hepatic damage resulting in the replacement elevation was noted on the ninth day of medication use [14].
of the healthy liver tissue by fibrosis and nodules, leading to This presentation normalized after discontinuation, but
loss of function over a period of several months [5]. returned again upon rechallenge.
Pharmaceutical injury to the liver is often idiosyncratic, Citalopram can cause hepatic enzyme elevation, with two
but it follows consistent patterns for individual medicines occurrences reported. One 56-year-old female, with no
and each drug group [2]. Idiosyncratic reactions occur in known liver disease and taking only citalopram, developed
hypersensitive (i.e., immunologic) or metabolic categories jaundice and elevated enzymes; liver biopsy revealed
[1]. Hypersensitivity reactions appear independent of the subacute dystrophy and cell necrosis [15]. Another vignette
medication dose, presenting 5–90 days following drug described a 44-year-old patient taking citalopram, clonaze-
initiation in an inflammatory and/or a cholestatic picture. pam and hydroxyzine who evidenced increased enzymes that
Continuing an offending agent is dangerous and can be fatal dramatically decreased after stopping only citalopram [16].
[2]. Features of a hypersensitivity reaction include fever, Otherwise, no disease progression was detected in subjects
cutaneous eruptions, eosinophilia and autoantibody forma- with hepatitis C who were prescribed citalopram [17]. Dose-
tion. Metabolic toxicity results from the biotransformation of dependent fatty liver infiltration is documented in rats [18].
the parent compound by hepatocytes to generate toxic Escitalopram is structurally related to citalopram and is
compounds in a dose-dependent fashion [1]; such problems thus expected to have a similarly safe side effect profile. No
are linked to a specific genetic polymorphism and have little cases of hepatotoxicity are known to have been recorded.
reproducibility from person to person [2]. Bupropion has been rarely associated with liver damage.
Drug-induced hepatotoxicity can present with inflamma- A 55-year-old man developed a fatal hepatotoxicity after 6
tion, cholestasis or mixed patterns [6]. With inflammation, months of therapy; he presented with jaundice and an
onset is acute, with severity ranging from nonsymptomatic autoimmune reaction after coadministration with other
cases of mildly elevated aminotransferase enzymes to pharmaceuticals [19]. A 41-year-old male with hyperthy-
fulminant liver failure. Those with jaundice and high roidism died of acute liver failure 10 days after starting
aminotransferases have the worst prognosis with a 10%– bupropion [20].
50% mortality rate, in a phenomenon known as Hy's rule [7]. Nefazodone has a “black box” warning for potential liver
Patients with cholestatic patterns have an elevated alkaline impairment and has been withdrawn from the market [21].
phosphatase. Hepatotoxicity may present acutely with Idiopathic liver failure resulting in death or transplant occurs
abdominal pain and fever resembling biliary obstruction or at a rate of one case per 250,000–300,000 patient-treatment-
chronically with jaundice and/or pruritus. These reactions years [22]. This rate is thought to be three to four times the
usually resolve gradually after drug withdrawal, but rarely risk experienced with similar drugs [22]. Hepatic impairment
can progress to ductopenic biliary cirrhosis and death [6]. was noted in 29 out of 100,000 patient-years of exposure
[23]. The literature describes three severe hepatic dysfunc-
tion cases requiring transplantation [24]. Nefazodone
2. Psychopharmaceuticals reportedly can induce mitochondrial toxicity [25].
2.1. Antidepressants Venlafaxine may induce idiosyncratic hepatotoxicity. A
60-year-old woman taking venlafaxine developed laboratory
Fluoxetine has a risk of a 0.5% incidence of causing abnormalities that resolved after medication discontinuation;
hepatic enzyme elevation [8]. There are at least 17 suspected a rechallenge resulted in a reoccurrence [26]. One man
cases of drug-induced liver injury reported. Four of them suffered fatal acinar liver cell necrosis after a venlafaxine
involved fluoxetine alone, and six shared coadministration overdose [27].
with another drug. Five individuals evidenced only minor Desvenlafaxine is relatively new to the market. It has been
enzyme abnormalities. Another 55-year-old man developed associated in rare instances with hepatic enzyme elevation
cholestatic liver injury with jaundice and pruritus after when used in high doses [28].
treatment with fluoxetine [9]. A 35-year-old male taking this Duloxetine is associated with several types of liver
agent developed chronic hepatitis [10]. injury, including hepatocellular, cholestatic and mixed
Paroxetine links to liver injury are found in at least 10 hepatocellular–cholestatic patterns [29]. Hepatobiliary dis-
published vignettes; sometimes these were cases in which ease is estimated to occur in about eight per 100,000 cases,
other medications were also prescribed [11]. An 84-year-old while enzyme elevations thrice the normal range are
woman with multiple medical problems and administered observed in 0.9%–1.7% of duloxetine-treated subjects
polypharmacy developed symptomatic hepatic damage after [29–31]. Idiosyncratic liver damage is estimated at one to
newly receiving paroxetine [11]. two per 100,000 case exposures [32].
 K. Sedky et al. / General Hospital Psychiatry 34 (2012) 53–61 55

Trazodone generally does not cause hepatotoxicity. Yet, reactions. Decades ago, due to impurities in the initial drug
there are at least six cases of acute or chronic hepatic damage formulation, jaundice was noted in up to 2% of cases, but
described [33]. A woman developed hepatotoxicity after when mild abnormalities were included, this rate increased to
8 months on trazodone; resolution of symptoms and decrease 42% [53]. With modern pharmaceutical modification,
in enzyme levels were observed 6 months after trazodone cholestatic chlorpromazine-induced jaundice is rare, but it
was discontinued [34]. still occurs in 0.16% of cases, and this increases to 0.3% in
Mirtazapine is usually safe; yet, dose-dependent enzyme persons over the age of 70 years [54]. Cross-reactivity
elevations have been reported [35]. Sporadic cases of between phenothiazines is rare. In patients treated with
hepatotoxicity are noted after long-term exposure [36]. perphenazine, 62% showed increases in liver enzymes levels.
Tricyclic/tetracylic antidepressant drugs are known to Only 4% of the individuals on this agent had three times or
cause hepatotoxicity, but few cases were reported lately, more elevation in these enzymes. Only 0.1% exhibited
possibly due to their relatively infrequent current use. twofold elevations in alkaline phosphatase, and 23% had a
Causality is not well established due to concurrent admin- onefold increase [55]. A dose-dependent acute cholestasis is
istration with other drugs and/or underlying liver disease documented in animals [54].
[21]. Tricyclic drugs might be more prone to causing such Butyrophenones rarely cause hepatotoxicity [54]. Halo-
damage than are the newer antidepressant agents [37]. In one peridol has been associated with threefold increases in
case, acute hepatitis developed with administration of the alkaline phosphatase in 0.3% of those treated, and a two-
tricyclic amineptine and recurred after taking clomipramine times elevation was observed in 0.8%. Half of those
[38]. Amineptine was withdrawn from the market due to receiving haloperidol developed some liver enzyme in-
hepatotoxicity. Prolonged cholestatic hepatitis developed in creases. Approximately 2.4% of patients had a threefold
one person on imipramine [39]. Iprindole, another older elevation in enzymes [55]. A two-times elevation in
tricyclic drug, is also associated with injury to the liver aminotransferases occurs in 17% of haloperidol-treated
[40,41]. A case of hepatotoxicity while on tricyclic individuals [56]. A 33-year-old patient developed allergic
antidepressants and phenothiazines was noted as a result of hepatotoxicity just weeks after haloperidol initiation [57].
treatment with trimipramine, desipramine and the neuroleptic Clozapine has been related to liver enzyme increase in
agent cyamemazine [42]. Acute hepatitis has been observed 30%–50% of patients; however, they were asymptomatic
after taking tianeptine [43]. Delayed elimination of amitrip- [58]. Icteric hepatitis occurs in 0.06% of those on clozapine,
tyline and its metabolites is seen after overdoses, possibly as compared to a more fulminant form occurring rarely at a
related to inflammatory toxicity [44]. Acute hepatitis rate of 0.001% [58]. This medication does raise hepatic
associated with the tetracyclic antidepressant maprotiline is enzymes [59]. Clozapine caused 37% of cases to show a
documented in a person also taking opipramol [45]. twofold or more increase in aminotransferases [56]. In a
Monoamine oxidase inhibitors (MAOIs), particularly the rechallenge with clozapine, a greater than three-times
hydrazine derivatives, can produce liver injury. Iproniazid, elevation in enzymes developed [60]. In a vignette about
an early MAOI, is no longer available and was never widely allergic hepatotoxicity, the patient reportedly became
used due to induction of hepatic necrosis [46,47]. Phenelzine clinically symptomatic and evidenced abnormal enzymes
reportedly has caused severe, acute and also chronic hepatic which improved after discontinuing the drug; treatment was
damage [47]. A 64-year-old woman treated with phenelzine successfully reinstituted at a lower dose [61]. A 30-year-old
developed an angiosarcoma [48]. Tranylcypromine, a patient had seizures and liver toxicity just days after
nonhydrazine MAOI, has once been cited as linked to increasing his clozapine dosage to 400 mg daily [62].
hepatic pathology [49]. Risperidone causes mild enzyme elevation in 53% of
Hepatotoxicity has not been associated with the use of cases, especially in aminotransferases, with severe elevations
selegiline. A reduced dosage may be required when selegiline in 0.8% [63]. A 17-year-old female developed enzyme
is prescribed to patients with abnormal liver function [50]. increase after treatment with clozapine that worsened after
changing to risperidone, but resolved after stopping both
2.2. Antipsychotic medications medicines [64]. There may be a male predisposition to such
an abnormality [65]. A diabetic individual evidenced
Antipsychotic medications have frequently been associ- elevated enzymes after 8 years on risperidone that resolved
ated with benign, transient increases in liver enzymes, and after its discontinuation [66]. Risperidone is metabolized
discontinuation is not usually required. Yet, severe hepatic mainly through cytochrome 2D6; thus, interactions with
damage is documented in rare instances. Checking baseline other pharmaceuticals can increase medication concentra-
liver functions and such monitoring during regular pharma- tions and toxicity. In a geriatric patient, acute cholestatic
cotherapy follow-up are sometimes recommended [51]. hepatitis developed a few days after adding risperidone to
Phenothiazines cause isolated increases in liver enzymes fluoxetine [67]. A risperidone-related immunological reac-
in up to 20% of patients, and overt hepatotoxicity occurs at a tion has also been documented in a person solely treated with
0.1%–1% rate [52]. Chlorpromazine is the most studied drug this agent [68]. A 6-week animal study has revealed a benign
in this regard and is associated with hypersensitivity pattern of injury [69].
56 K. Sedky et al. / General Hospital Psychiatry 34 (2012) 53–61

Paliperidone is a metabolite of risperidone and not likely rare, but reported [93]. During a 7-year follow-up of one
to cause liver impairment, but it is new to the market. It is million prescriptions, 29 fatal hepatotoxicity cases were
excreted mainly by the kidney and has no known identified. Young age, especially under 2 years old; use of
metabolites. Paliperidone may be preferred for treating multiple medications; presence of neurological disorders
psychotic patients with a compromised hepatic status [70]. and/or metabolic abnormalities increase the risk of injury
Olanzapine is frequently associated with transient liver [94]. Especially in people with carnitine deficiency,
enzyme elevations. This may not require medication valproate products can induce a hyperammonemic enceph-
discontinuation [71,72]; the incidence rate of 9% was not alopathy [95]. This can occur unrelated to liver enzymes or
dose dependent [73]. Isolated, serious damage cases with valproate blood levels [96]. These drugs should be avoided
transaminases reaching up to 10 times the normal range have in persons with mitochondrial diseases since this might result
been described [74]. Olanzapine was associated with liver in liver failure [97]. Divalproex may induce polycystic
dysfunction in 27% of treated cases [75]. Hepatotoxicity was ovarian disease and thus increase steroid concentrations that
also documented in animal studies [76]. might have been related to a hepatocellular adenoma [98].
Quetiapine sporadically causes liver damage [66]. Acute One 64-year-old female on divalproex for 17 years has
injury was described with full resolution after steroid therapy developed nonalcoholic steatosis and a hepatocellular
[77]. A 30-year-old man developed cholestasis while taking carcinoma [99].
risperidone with quetiapine [66]. Another patient died of The safety of divalproex was reviewed in individuals
hepatic failure [78]. Quetiapine is metabolized by the having hepatitis C [100]. Although subjects medicated with
cytochrome enzymes CYP P450 3A4 and 2D6 [79], and this agent had a higher frequency of elevated enzyme levels,
use of only small increments of dosage increase is advised they were often safely taken without complications.
when using this medication in hepatically compromised Lamotrigine has been associated with hepatic inflamma-
individuals [80]. tion in one per 1000 treated cases [101]. In rare occasions, it
Ziprasidone blood levels evidence a mildly prolonged resulted in fulminant liver failure [102]. In a patient treated
duration of action in people with compromised liver function. with oxcarbazepine, elevated enzymes occurred after the
It has nevertheless been safely used in this population [81]. addition of lamotrigine and resolved after its discontinuation
Aripiprazole package inserts recommend cautious use in [103]. A 21-year-old man receiving aripiprazole and
liver disease cases. However, the manufacturer has not lamotrigine developed elevated enzymes which normalized
suggested dosage adjustment [82,83]. after stopping lamotrigine [101].
Topiramate is mainly excreted through the kidneys, but
2.3. Mood stabilizers hepatitis and liver failure have been associated with its use. A
51-year-old woman taking divalproex developed reversible
Carbamazepine can precipitate considerable hepatotoxicity. liver toxicity after topiramate was added to her regimen
It is a potent inhibitor of CYP P450 3A4 and also an enzyme [104]. Acute hepatic failure occurred in another case [105].
inducer, even an autoenzyme inducer to its own metabolism. High doses of topiramate have yielded hepatotoxicity in
Baseline and ongoing laboratory monitoring is indicated. animal studies [106].
Coadministration with other hepatotoxic medications can Gabapentin is mainly excreted by the kidney; adverse
predispose to severe liver damage [84]. Carbamazepine is also effects on the liver are rare. Yet, a case of cholestasis [107]
associated with hyperammonemia [85]. Stevens–Johnson and another of hepatotoxicity with eosinophilia were
syndrome, characterized by skin exfoliation, fever, lymphade- reported in persons taking this medication [108].
nopathy with eosinophilia and hepatitis, is also occasionally Pregabalin is mainly excreted through the kidneys [109].
described, even with fatal consequences [86,87]. Mothers Nevertheless, suspected toxic effects to the liver have been
using this agent birthed infants with liver impairments. One reported [110].
neonate experienced asphyxia and transient hepatic dysfunc- Lithium is considered safe due to its renal excretion;
tion [88]. Carbamazepine clearly has greater risks for liver however, there has been a single case report of a patient with
damage than most other psychiatric drugs. elevated hepatic enzymes associated with lithium [111].
Oxcarbazepine, a newer pharmaceutical, might have Another vignette describes ascites [112]. One instance of
greater liver safety compared to its parent drug, carbamaz- severe lithium poisoning was reported to have occurred
epine. A 28-year-old male with porphyria and epilepsy had along with newly elevated enzymes in an alcoholic patient
abnormal enzymes while prescribed carbamazepine, which [113]. Hyperbilirubinemia was documented in someone
normalized once it was replaced by oxcarbazepine [89]. This taking lithium [114].
drug has been associated with a hepatoadenoma in animals
and in one human case [90]. An oxcarbazepine-induced 2.4. Anti-addiction psychopharmaceuticals
Stevens–Johnson syndrome with liver dysfunction was
documented in an 11-year-old child [91]. Methadone is linked to hepatotoxicity [115]. Coadminis-
Divalproex can result in steatosis in up to 60.9% [92] tration of ethanol potentiates opioid-induced hepatotoxicity
cases. Hypersensitivity reactions to all valproate products are [116]. Methadone was safe in a small study of methadone
 K. Sedky et al. / General Hospital Psychiatry 34 (2012) 53–61 57

maintenance in subjects with a history of heroin addiction 2.6. Anti-dementia drugs

and who underwent liver transplant due to a different
etiology of their liver disease [117]. Tacrine causes transaminase elevations in 50% of cases,
Buprenorphine-induced hepatitis is an uncommon phe- with significant increases in 25%. Patients were almost
nomenon, even if it is misused via the intravenous route always asymptomatic, with 90% of the toxicities occurring
[118]. Four cases with marked increases in enzymes have in the initial 12 weeks of pharmacotherapy [133].
been reported in people who were former heroin addicts and Rechallenge with this agent was successful 88% of the
who had a history of hepatitis C infection after they injected time [134]. This adverse effect was more often noted among
buprenorphine intravenously. Discontinuation of buprenor- females. Although rare, tacrine has been associated with
phine injections was associated with prompt recovery, even fatal liver damage and death. Jaundice and severe
though two of them continued buprenorphine sublingually. impairment developed 14 months after treatment with
Jaundice and asterixis with pan-lobular liver necrosis and tacrine in a 75-year-old lady who was receiving other
microvesicular steatosis were noticed in another patient with hepatotoxic medication [135]. Diverse histological abnor-
the hepatitis C and human immunodeficiency viruses after malities of granulomatous hepatitis, centrilobular cell
using sublingual buprenorphine along with acetaminophen necrosis and mild fatty change have also been documented
and aspirin [118]. on liver biopsy [136].
Naltrexone carries a “black box” warning for hepatotox- Donepezil has only rarely been related to hepatotoxicity.
icity when used in excessive quantities, but it is not observed Jaundice and acute liver toxicity developed in an elderly
at recommended doses. Naltrexone is contraindicated in woman when donepezil was coprescribed with sertraline
people with liver failure or acute hepatitis. One case study [137]. Toxic hepatitis was reported in another patient
demonstrated mild enzyme elevations that normalized with treated with donepezil [138]. Rivastigmine has been
continued therapy [119]. Monthly liver enzyme checking is associated with mixed cholestatic and hepatocellular injury
indicated during treatment with this agent. in one instance [139]. Memantine-induced hepatitis with
Abnormal liver function tests associated with disulfiram cholestasis is described in one elderly individual [140].
may be more indicative of alcohol consumption rather than There are no known reports of hepatotoxicity associated
drug-induced hepatitis, but such findings do occur in nearly with galantamine [141].
one out of every 25,000 cases annually [120]. A 23-year-old
person, however, developed liver failure after treatment with 2.7. Anxiolytic agents
this agent [121]. The value of obtaining baseline and routine Benzodiazepine-induced liver injury is rare and is classified
follow-up enzyme levels while on disulfiram maintenance as an unpredictable or idiosyncratic reaction. A few cases of
remains controversial [120]. cholestatic reaction have been documented following the use
of diazepam, chlordiazepoxide and flurazepam. Case reports
2.5. Attention-deficit/hyperactivity medications also describe hepatocellular injury with bentazepam, a
benzodiazepine available in Europe [142]. No evidence was
The severity of pemoline-associated hepatotoxicity may found which linked buspirone to liver toxicity.
vary from asymptomatic enzyme elevations to fulminant
liver failure [122]. A liver transplant was required in one 2.8. Herbal remedies
reported case. Pemoline can induce hepatotoxicity, and
several case reports support this impression [123–128]. Many people consider herbal supplementations as being
These concerns led to the conclusion that the potential risks safe. Among the herbal agents used to treat psychiatric
associated with treatment outweighed the benefits; this conditions, kava kava is the most hepatotoxic agent.
subsequently led to the withdrawal of pemoline from the Although controversies exist around the hepatotoxicity of
market [129]. this agent, many European countries banned its use. The
Atomoxetine has been associated with liver injury, US Food and Drug Administration has warned about this
especially during the first 120 days of treatment. Enzymes potential. Analysis in many cases revealed a higher
increased up to 20 times the usual range, and bilirubin levels prevalence in individuals taking more than the recom-
were more than twice normal [130]. The manufacturer mended dosage, those with prolonged use and/or those
recommends discontinuation without rechallenge if such combining it with other hepatotoxic agents [143]. In a
injury occurs [130]. Out of 7961 subjects treated with 14-year-old female with no known medical problems,
atomoxetine in clinical trials, 41 had a hepatic adverse event, symptomatic fulminant hepatitis occurred within 4 months
although none of them developed liver failure [131]. Four while just on kava kava. This person and three others required
years after marketing, 351 hepatotoxicities were reported, of liver transplantation [144]. Analysis of data suggested a
which three were associated with atomoxetine; stopping the 0.008 per million cases of toxicity for every daily user of this
drug resulted in recovery. An 8-year-old girl developed herb [145].
hepatic inflammation that improved after atomoxetine Valeria, another anxiolytic herbal supplement, has rarely
discontinuation [132]. been linked to acute and chronic liver insult [146]. Other
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