Skip to main content

Special considerations in the treatment of patients with bipolar disorder and medical co-morbidities



The pharmacological treatment of bipolar disorder has dramatically improved with multiple classes of agents being used as mood-stabilizers, including lithium, anticonvulsants, and atypical antipsychotics. However, the use of these medications is not without risk, particularly when a patient with bipolar disorder also has comorbid medical illness. As the physician who likely has the most contact with patients with bipolar disorder, psychiatrists must have a high index of suspicion for medical illness, as well as a basic knowledge of the risks associated with the use of medications in this patient population.


A review of the literature was conducted and papers addressing this topic were selected by the authors.

Results and discussion

Common medical comorbidities and treatment-emergent illnesses, including obesity, diabetes mellitus, dyslipidemia, cardiac disease, hepatic disease, renal disease, pulmonary disease and cancer are reviewed with respect to concomitant use of mood stabilizers. Guidance to clinicians regarding effective monitoring and treatment is offered.


Mood-stabilizing medications are necessary in treating patients with bipolar disorder and often must be used in the face of medical illness. Their safe use is possible, but requires increased vigilance in monitoring for treatment-emergent illnesses and effects on comorbid medical illness.


Patients with bipolar disorder are among the most challenging to treat pharmacologically, especially in the presence of medical comorbidity. Although the rates of medical comorbidity are high in patients with bipolar disorder (20–80%), medical illnesses are frequently underdiagnosed and inadequately treated in psychiatric patients. For example, Cradock-O'Leary and colleagues reviewed centralized Veterans Affairs data and examined the use of medical services by 175,653 veterans during fiscal year 2000 [1]. They identified 3,694 veterans with a primary diagnosis of bipolar disorder and compared the care that these veterans received to that of all veterans. Among all veterans with diabetes and hypertension, those with a comorbid diagnosis of bipolar disorder (as well as those with diagnoses of anxiety disorder, schizophrenia, post-traumatic stress disorder, or a substance use disorder) were less likely to have more than one medical visit in one year. This is especially concerning given that veterans are afforded medical and psychiatric treatment within one comprehensive health care system, seemingly making care more accessible. Patients with bipolar disorder in the general population are likely receiving even less medical care. The significance of this finding is that the psychiatrist may be the only physician caring for these patients on a regular basis. Therefore, psychiatrists must have a high index of suspicion for medical illness, as well as a basic knowledge of the risks associated with the use of medications in this patient population.

The purpose of this paper is to identify common medical comorbidities in bipolar disorder, including those that are treatment–emergent, and to offer guidance to clinicians regarding effective monitoring and treatment.

Material and methods

An extensive review of effective pharmacotherapies is beyond the scope of this paper which will perform a selective review of the psychotropic medications often prescribed to patients with bipolar disorder, with an emphasis on their use in patients with medical comorbidity. More specifically, the review results include papers concerning bipolar patients with obesity, diabetes mellitus, dyslipidemia, cardiac, hepatic, renal and pulmonary disease and cancer.

It is essential to keep in mind that benefit cannot be deleted from the risk:benefit analysis. In some cases a medication with greater side effects or medical risk may be the preferred treatment because of the documented efficacy of the agent either in general, or in a particular patient.

This paper will perform a selective review of the psychotropic medications often prescribed to patients with bipolar disorder, with an emphasis on their use in patients with medical comorbidity. Currently, lithium, valproate, olanzapine, lamotrigine, risperidone and quetiapine are indicated for use in bipolar disorder by the US Food and Drug Administration (FDA). Aripiprazole has recently been submitted to the FDA for approval in the treatment of bipolar disorder. Other agents are also used as adjuncts, despite limited efficacy data. As such, mention of a medication in this article does not necessarily imply efficacy, and the reader is referred to the American Psychiatric Association practice guideline for Bipolar Disorder (2002).

Results and discussion


Obesity is a leading cause of preventable death in the United States, with an estimated 300,000 people dying annually of obesity-related causes [2]. Although the general population in the United States is increasingly more overweight and obese, 64.5% and 30.5%, respectively, in a 1999–2000 survey, individuals with bipolar I disorder are still slightly more likely to be obese [3]. Fagiolini and colleagues found that 35.4% of patients with bipolar disorder were obese. Pharmacotherapy and affective episodes both influence appetite and physical activity, thereby increasing the risk for obesity. Obesity in bipolar patients is correlated with a greater number of lifetime depressive and manic episodes, a more severe and difficult-to-treat index episode, and a greater risk of developing an affective recurrence, most often depression [4].

Persons with bipolar disorder are more likely to be overweight (body mass index [BMI] of 25–29.99 kg/m2) or obese (BMI of 30 kg/m2 or greater) even when mood is euthymic. Elmslie and colleagues found the prevalence rates for obesity and being overweight in euthymic female bipolar patients were 1.5 and 1.8 times greater, respectively, when compared to the reference group [5]. Obesity was also more prevalent in male euthymic patients compared with the reference group. In both male and female bipolar patients, truncal obesity was most prominent. This pattern of obesity reflects fat that is distributed centrally between the thorax and pelvis and is associated with increased risk of type 2 diabetes mellitus, dyslipidemia, hypertension, stroke, ischemic heart disease and early mortality [69]. The authors concluded that the prevalence of obesity in this study of outpatients was related to the use of antipsychotics, but less so lithium or anticonvulsants. Of those persons prescribed no psychotropics, less than 10% were obese, suggesting that bipolar disorder itself does not cause obesity, and that pharmacologic treatment and gender are greater influences [10].

Important factors influencing obesity in bipolar patients include nutrient intake and physical activity. In assessing the nutrient intake of persons with bipolar disorder, Elmslie and colleagues found that they had increased intake of carbohydrates and sweets, especially non-alcoholic sweetened drinks [5]. The intake of sucrose was higher in patients, particularly females, receiving antipsychotics than in those receiving other or no medications. Patients with bipolar disorder were also more sedentary, exercising less frequently and with less intensity than reference subjects. Medication side effects such as dry mouth and increased thirst may lead to increased consumption of sweetened drinks. Sedation, decreased motivation and impaired coordination may promote physical inactivity.

Obesity in patients with bipolar disorder should not be the only factor used to inform selection of psychotropics. In fact, patients who are obese at baseline may be less likely to have significant weight gain than those with a lower baseline body mass index. At the same time, though, use of certain psychotropic medications may make it more difficult for those patients to lose weight. Patients should be weighed at baseline and again two weeks after beginning treatment. If the patient gains four pounds or more, behavioral interventions of diet and exercise and a consultation with a nutritionist should be considered. Specific dietary modifications should include avoidance of refined carbohydrates, including sweetened drinks, increased intake of omega-3 fatty acid, and small amounts of protein with each meal [11]. Behavioral interventions can lead to significant loss of weight gained while taking atypical antipsychotics, and the modifications of eating and exercise habits help patients maintain the weight loss [12].

Pharmacologic treatment of obesity should be avoided if at all possible, given the risk of side effects and drug interactions. Pharmacologic agents should be reserved for those patients with a BMI of 30 kg/m2 or greater, or a BMI of 27 kg/m2 or greater and risk factors for weight related medical illnesses [12]. Agents associated with weight loss include metformin [1315], topiramate [16], sibutramine [12], amantadine [18, 19], nizatidine [19] and orlistat [20]. Centrally acting agents have a theoretical risk of exacerbating psychosis or mood disorders and should be used with caution [22, 23].

Gastric restrictive surgical interventions may be considered for patients whose BMI exceeds 40 kg/m2 and who have not responded to behavioral interventions or pharmacologic treatment [12].

Diabetes mellitus

Cassidy and colleagues reported the prevalence of diabetes mellitus in hospitalized bipolar patients to be approximately three times the national average [24]. Further, bipolar patients with diabetes mellitus had more lifetime psychiatric hospitalizations than non-diabetic bipolar patients. It is prudent, therefore, for psychiatrists to be aware of the risk factors associated with diabetes, including treatment-emergent diabetes. Recent publications linking atypical antipsychotics with treatment-emergent diabetes are numerous, but often contradictory. There are reports of hyperglycemia associated with risperidone, quetiapine and ziprasidone, and more frequently with clozapine and olanzapine [26, 27].

Of note, those with baseline risk factors for diabetes mellitus are more likely to develop treatment-emergent diabetes (TED). Sowell identified risk factors for patients who entered clinical trials and later developed TED [28]. At study entry these patients had higher random glucose levels, were older, more obese and more likely to possess multiple risk factors for DM. Neither treatment-emergent weight gain nor treatment group significantly impacted the risk for TED. Established risk factors for diabetes include: family history, ethnicity, increasing age, central obesity, physical inactivity, low HDL/high triglycerides, fasting glucose of 110 mg/dL or greater, gestational diabetes, hypertension, and polycystic ovary syndrome.

Though questions remain about the pathophysiology of treatment-emergent diabetes, guidelines are being formulated to aid clinicians in identifying patients at risk. Screening for diabetes should include questioning patients about symptoms such as excessive thirst and urination, nocturia, unexplained weight loss, fatigue, frequent infections, and blurred vision. Recommendations for fasting glucose screening at baseline and follow-up for patients receiving atypical antipsychotics are presented in Table 1[29].

Table 1 Diabetes Mellitus Screening Recommendations For Patients Treated with Atypical Antipsychotics [29]


The effects of atypical antipsychotics on lipid levels have been reported primarily in patients with schizophrenia. Studies of patients on atypical antipsychotics, as well as high potency neuroleptics, show a significant association between weight gain and cholesterol and triglyceride elevation in patients with schizophrenia. This association is most commonly observed in patients prescribed clozapine and olanzapine, reaching statistical, though not necessarily clinical significance [26, 3033]. Olanzapine, risperidone and quetiapine have also been shown to decrease mean low-density lipoprotein (LDL) levels, and olanzapine may also lower mean high-density lipoprotein (HDL) levels [30]. Some studies indicate that ziprasidone may lower cholesterol and serum triglycerides [27]. As such, some authors recommend monitoring body weight, fasting cholesterol and triglycerides at baseline and every six months in routine clinical practice with all antipsychotics [26].

The effects of anticonvulsants on serum lipid and cholesterol levels have been studied primarily in patients with seizure disorders. Carbamazepine-induced increase in total cholesterol is primarily due to an increase in HDL [34]. This occurs during the initial weeks of therapy, persists throughout treatment and reverses in the first few weeks after discontinuation. A 5-year prospective study of patients treated with carbamazepine also revealed a transient increase in LDL cholesterol and triglycerides in the first year of treatment [35]. When carbamazepine was replaced with oxcarbazepine in patients with seizure disorders, total serum cholesterol levels decreased, but HDL cholesterol and triglyceride levels remained unchanged [36].

Women with obesity and polycystic ovaries or hyperandrogenism treated with valproate have also been shown to have elevations in serum triglycerides and low HDL to total cholesterol ratios [37, 38]. This is consistent with insulin resistance in this population. Valproate does not appear to contribute to clinically significant dyslipidemia across other populations [38, 39]. The effects of lamotrigine and topiramate on serum cholesterol and triglyceride levels have been reported in small studies and case reports [16, 38]. Neither of these anticonvulsants appears to affect lipid levels.

Currently there are no published recommendations for monitoring serum lipids in patients receiving anticonvulsants. In patients identified as having polycystic ovaries or hyperandrogenism, monitoring of lipid levels is warranted.

Cardiac disease

As discussed above, patients with bipolar disorder have a higher prevalence of cardiac risk factors, such as obesity, glucose dysregulation and dyslipidemia. It is not surprising, therefore, that patients with bipolar disorder also have greater mortality from cardiovascular disease compared with the general population [40]. Further, many of the medications that treat bipolar disorder may have cardiac side effects or toxicity. Underlying cardiac disease may also affect the pharmacokinetics of psychotropics.

Congestive heart failure (CHF) can affect pharmacokinetics in various ways. Diminished cardiac output results in a shift of blood flow to vital organs. This may lead to decreased perfusion of the gastrointestinal tract and skeletal muscle with resultant erratic absorption of oral and intramuscular medications, increased drug delivery to brain tissue, reduced blood flow to kidneys with resultant slowed clearance and prolonged elimination half-lives. Though studies supporting dosing guidelines for psychotropics in CHF are lacking, it has been recommended that medication doses be reduced by 50% in patients with CHF [41].

Lithium has been shown to both induce and ameliorate CHF. In therapeutic doses, lithium probably does not decrease cardiac contractility. However, if CHF symptoms worsen, lithium should be discontinued [42]. Patients with CHF are also at increased risk for orthostatic hypotension, specifically with medications that antagonize alpha-1 receptors [43]. Medications with significant alpha-1 blockade include low-potency neuroleptics and atypical antipsychotics (quetiapine > risperidone > olanzapine/ziprasidone). Lithium and anticonvulsants are not alpha-1 antagonists [44].

Patients with preexisting intraventricular conduction delays are at increased risk for complete heart block when given medications with quinidine-like properties, including carbamazepine and tricyclic antidepressants [45]. Valproate has no known adverse cardiac effects [46]. Lithium is associated with sinus node dysfunction, which is usually reversible with discontinuation of medication [42]. There is sparse evidence for first-degree atrial-ventricular (AV) block and rare reports of aggravation of ventricular arrhythmias with lithium at therapeutic levels. However, lithium toxicity may be associated with sinoatrial block, AV block, AV dissociation, bradyarrhythmias, ventricular tachycardia, and ventricular fibrillation. T-wave flattening or inversion with therapeutic lithium levels are of uncertain clinical significance and are usually reversible upon discontinuation of lithium therapy [42].

Prolongation of the QTc interval on electrocardiograph (ECG) in the context of antipsychotic medication use has received increased attention in recent years. Prolongation of the QT interval greater than 500 ms increases the risk of torsade de pointes, a polymorphic ventricular tachycardia that is associated with syncope and sudden death. Several antipsychotics have been documented to cause torsade de pointes and sudden death, including pimozide, sertindole, droperidol, haloperidol, and thioridazine, which has the greatest risk [47]. Risperidone-induced QT prolongation has been observed, including one fatality, though torsade de pointes was not reported [48]. Ziprasidone has also been associated with prolongation of the QT interval; however, to date, no cases of ziprasidone-associated torsade de pointes or sudden death have been reported in the literature or to the Federal Drug Administration. It should be pointed out, though, that most of the safety data on ziprasidone to date originates from clinical trials, with selective entry criteria likely to exclude patients who are susceptible to torsade de pointes and sudden death.

A study of the effects of six antipsychotics on the QT interval found that thioridazine produced the most prolongation (mean change of 35.6 ms), followed by ziprasidone (20.3 ms), quetiapine (14.5 ms), risperidone (11.6 ms), olanzapine (6.8 ms), and haloperidol (4.7 ms) [47, 49, 50]. These findings are difficult to interpret given that quetiapine and olanzapine have not been implicated in cases of torsade de pointes or sudden death, but produced greater prolongation than haloperidol, which has been associated with the fatal arrhythmia.

At this time, routine ECG screening and monitoring has not been recommended before initiating treatment with antipsychotics. However, a careful medical history should be taken for symptoms of cardiac pathology, such as recurrent syncope. A family history of early sudden death should be obtained and serum electrolyte imbalances should also be corrected as these may predispose patients to arrhythmias. It has been suggested that ECG monitoring be undertaken in patients at higher risk, including those with cardiovascular disease, a history of QT prolongation, polypharmacy (metabolic inhibitors or other drugs known to affect the QT interval), high doses of antipsychotics, or symptoms possibly related to arrhythmias (syncope, palpitations, dizziness, etc.). The QTc interval may not reliably predict the risk for arrhythmia; however, an examination of the ECG by a cardiologist for other signs of arrhythmia may facilitate a more useful assessment of risk [50].

Patients with recent myocardial infarction (MI) are at increased risk for arrhythmias, heart failure and sudden death and are frequently treated with numerous medications, thereby increasing the likelihood for drug interactions with psychotropic medications. Lithium may be used after MI, but care must be taken to monitor for and correct any electrolyte aberrations. Of note, lithium in combination with angiotensin converting enzyme (ACE) inhibitors may produce an increased risk of arrhythmia [42, 51]. Valproate has an increased risk of liver injury in conjunction with lipid-lowering agents, as well as risk of bleeding complications when taken with antiplatelet agents, warfarin or niacin. Carbamazepine acts as an inducer of cytochrome 3A4, which may increase the metabolism of some anticoagulant and cardiovascular medications. Olanzapine may induce or worsen cardiac risk factors such as obesity, metabolic derangements and hyperlipidemia. Quetiapine and risperidone may also contribute to obesity. Ziprasidone should be avoided due to increased risk of arrhythmia [51]. Cardiovascular condsiderations in the treatment of bipolar disorder are reviewed in Table 2.

Table 2 Cardiovascular Considerations in the Treatment of Bipolar Disorder

Hepatic disease

Patients with pre-existing liver disease are at increased risk for liver toxicity due to psychotropic medications. Hepatic insufficiency increases blood levels and half-lives of all psychotropic medications, except lithium. Possible mechanisms include: decreased oxidative metabolism through cytochrome enzymes; possible reduction of conjugation pathways for medications that predominantly undergo glucuronidation; decrease in hepatic blood flow because of portacaval shunting, thereby decreasing first pass metabolism; decrease in quantities and affinity of plasma proteins, thereby increasing free-drug levels; increase in volume of distribution in patients with ascites [52].

Hepatitis C virus (HCV) infection is a leading cause of cirrhosis and liver transplantation in the United States, with an estimated prevalence of 3 million Americans [53]. There is a high comorbidity between hepatitis C and psychiatric illness. Computerized chart reviews of HCV-infected veterans revealed that 86.4% had at least one past or present psychiatric, drug or alcohol-abuse disorder, and 31% had active disorders as defined by recent hospitalizations to psychiatric or drug-detoxification units [54]. Given the high comorbidity of HCV and psychiatric illness, we must use caution in prescribing psychotropics with known hepatotoxicity, especially anticonvulsants. However, these medications are not necessarily contraindicated.

Some authors have reported that alanine aminotransferase (ALT) elevation was not significantly greater when starting treatment with valproate as compared to antidepressants, lithium or gabapentin in patients with HCV [55]. These findings suggest that valproate can be used for some patients with HCV without adversely affecting ALT levels. Obtaining pretreatment baseline ALT levels in patients with HCV is recommended as well as monitoring of levels during treatment. Discontinuation of valproate when aminotransferase levels are "clearly increased above the normal pretreatment baseline" is recommended [55].

Many patients (10–40%) receiving valproate will experience a reversible increase in aminotransferases. Valproate-induced liver injury occurs with a frequency of approximately 1 per 37,000 persons exposed [56]. Certain groups have an increased risk of 1 per 500, including those with personal or family history of mitochondrial enzyme deficiency, Reye's syndrome, Friedreich's ataxia, a sibling affected by valproate hepatotoxicity, or multiple drug therapy, as well as children younger than 3 years of age [57].

Several anticonvulsants have been associated with anticonvulsant hypersensitivity syndrome (reactive metabolite syndrome), including carbamazepine, phenytoin, phenobarbital, and lamotrigine. The triad of hypersensitivity includes fever, rash and internal organ involvement with onset of symptoms within 1 to 8 weeks of exposure. The frequency of the syndrome is estimated at 10–100 per 100,000 persons exposed. Risk of serious hypersensitivity reactions among first-degree relatives of those who have had a reaction to one of these anticonvulsants is about 1 in 4 [5759].

There are case reports of hepatic injury associated with other drugs that are commonly used in bipolar disorder. There have been a few case reports linking olanzapine with acute hepatocellular injury and one of acute hepatitis accompanied by hallmarks of a hypersensitivity syndrome [57]. Risperidone may cause transient increases in aminotransferases as well as cholestatic hepatitis [57], but hepatic disease does not appear to modify drug pharmacokinetics [60]. Topiramate has been associated with one case report of acute hepatic failure in a woman who was also treated with carbamazepine, as well as one case of reversible ALT elevation [57].

Recognizing early symptoms of hepatic toxicity and discontinuing treatment are important in optimizing recovery. Early symptoms of hepatic toxicity include apathy, malaise, fever, diminished appetite, nausea, and vomiting [63]. Regular monitoring of aminotransferases may also help identify patients with "silent" hepatotoxicity. Referral to an internist or hepatologist, following discontinuation of the offending agent, is warranted if treatment-induced liver injury is suspected. If symptoms of anticonvulsant hypersensitivity syndrome are apparent, the patient should be referred for emergency treatment. Dosage adjustments for patients with hepatic disease are shown in Table 3.

Table 3 Recommended Dosage Adjustments for Patients with Comorbid Hepatic and Renal Disease

Renal disease

The prevalence of chronic kidney disease in the adult population of the United States is 11% (19.2 million people) [64], and as death rates from heart disease, cancer and pneumonia decrease, deaths from renal disease are on the rise [65]. As more of our patients develop renal disease, psychiatrists must be aware of the effects of psychotropics on the kidneys, as well the effects of decreased renal functioning on the pharmacokinetics of medications prescribed.

Of all the medications used to treat bipolar illness, lithium has the greatest effect on the kidney. Lithium is associated with an impaired urinary concentrating capacity resulting in polyuria that can, rarely, become permanent due to irreversible structural tubular damage [42, 66]. Glomerular function is less affected by lithium. Nephrotic syndrome occurs rarely at therapeutic lithium levels. If this does occur, lithium discontinuation alone or in combination with diuretics, hemodialysis, or steroids generally results in improvement [67]. Renal tubular acidosis (RTA) has also been associated with lithium use and is more likely in patients with other conditions (medullary sponge kidney, carbonic anhydrase B deficiency, tubulointerstitial nephropathy), medications producing acidosis (amphotericin B, non-steroidal anti-inflammatory drugs [NSAIDs]), or urinary acidification defects [42].

Patients with preexisting kidney disease are at increased risk for lithium toxicity and possibly the nephrotoxic effects of lithium. Lithium is contraindicated in acute renal failure, though chronic renal failure is not an absolute contraindication with close monitoring. It has been recommended to maintain lithium levels between 0.6 and 0.8 mEq/L in this setting [42]. Lithium may be used in patients on hemodialysis (HD) and should be administered in a single post-dialysis dose of 300–600 mg. Lithium levels should be checked pre-dialysis and 2–3 hrs following the post-dialysis dose. There is a case report in which lithium levels were maintained in the therapeutic range by intraperitoneal administration of lithium during continuous peritoneal dialysis [68].

Lithium has been used safely in post-renal transplant patients. Living-related-donor allograft recipients show near normal renal function within hours after transplant and lithium dose may be increased by the first post-transplant day. Cadaveric allograft recipients frequently develop acute tubular necrosis (ATN) with fluctuating renal function causing inconsistent serum levels and increased risk of toxicity [69]. Antirejection drugs also affect lithium levels: methylprednisolone decreases tubular reabsorption of lithium and cyclosporine decreases excretion of lithium [42].

Pharmacokinetics of some medications are altered by nephrotic syndrome due to low levels of serum albumin and higher levels of unexcreted metabolites competing for protein binding sites, resulting in increased bioavailability of free, active highly protein-bound drugs. Accumulation of active hydroxylated metabolites of carbamazepine may lead to symptoms of drug toxicity despite therapeutic drug levels [70].

Renal insufficiency and failure result in decreased drug clearance for many psychotropics. Valproate clearance is diminished by 27% in renal failure; however, it is cleared by hemodialysis (HD) so no dose adjustment is recommended [71]. The elimination half-life of lamotrigine is prolonged in renal failure, and dosing may need to be modified based on the creatinine clearance [72, 73]. Gabapentin clearance is linearly related to creatinine clearance and dose should be decreased accordingly [74]. Topiramate clearance is decreased and the elimination half-life is prolonged with renal impairment. It is recommended that half the usual adult dose be used in renally impaired patients. Further, topiramate is a weak carbonic anhydrase inhibitor and is associated with the development of renal calculi. In clinical trials, 1.5% of patients treated developed renal stones. This risk can be reduced with adequate hydration [75]. Risperidone clearance is decreased by 60% and half-life increased in moderate to severe renal disease, though it is cleared by HD. Dosage adjustment is recommended in renal disease [60]. The pharmacokinetics of olanzapine, quetiapine, and oral ziprasidone are not altered in renal disease [76, 77]. Though the intramuscular formulation of ziprasidone has not been studied in patients with renal impairment, because the cyclodextrin excipient is renally cleared it is suggested that it be administered with caution to patients with renal impairment [78]. Suggested dosage adjustments for medications used in the context of renal disease are shown in Table 3.

Pulmonary disease

There are few reports of mood stabilizers and atypical antipsychotics contributing to respiratory depression or pulmonary disease. One case report of olanzapine-associated respiratory failure occurred in an elderly patient with chronic lung disease and the authors recommend careful observation of patients with chronic lung disease treated with olanzapine [79]. In the clinical trials of quetiapine, hyperventilation was reported to occur in <1/1000 patients treated and case reports have appeared in the literature [80]. Lithium, anticonvulsants, risperidone and ziprasidone do not appear to alter respiratory drive.


Patients with cancer are particularly susceptible to the hematologic and cognitive effects of medications, due to both their illness and chemotherapeutic treatment. Lithium should be closely monitored as fluid and electrolyte intake may vary in patients with cancer. Close monitoring is also necessary when lithium is combined with nephrotoxic chemotherapeutic agents such as cisplatin. An increased risk of cognitive dysfunction with lithium, especially in patients with primary brain tumors or metastasis has been reported. Carbamazepine has a risk of marrow suppression, which may produce an additive effect when combined with chemotherapeutic agents that suppress blood marrow production. Valproate, risperidone and olanzapine have been safely used in patients with cancer [81]. Olanzapine has been studied in patients with cancer and has been found to have an antiemetic effect [82], as well as reducing pain scores and opioid requirements in patients with uncontrolled cancer pain associated with cognitive impairment or anxiety [83].


The treatment of bipolar disorder is complicated in patients with medical comorbidity. Patients with psychiatric illness may not have routine general medical care and diagnosis of general medical conditions may be delayed. As the physician with the most (and often the only) contact with these patients, psychiatrists need to be vigilant in detecting early signs and symptoms of medical illness and facilitating referral for appropriate evaluation and intervention. Psychiatrists must also be aware of the medical risks of psychotropic medications and their use in the medically ill population. This paper has reviewed some of the medications commonly used in bipolar disorder and discussed their use with comorbid medical illness.

Drug names

Amantadine (Symmetrel), amphotericin B (Amphocin and Fungizone), aripiprazole (Abilify), carbamazepine (Tegretal and others), clozapine (Clozaril), droperidol (Inapsine and others), gabapentin (Neurontin), haloperidol (Haldol and others), lamotrigine (Lamictal), lithium (Eskalith and others), metformin (Glucophage), nizatidine (Axid), NSAIDs (Ibuprofen, Naproxen and others), olanzapine (Zyprexa), orlistat (Xenical), oxcarbazepine (Trileptal), phenytoin (Dilantin and others), pimozide (Orap), quetiapine (Seroquel), risperidone (Risperdal), sibutramine (Meridia), thioridazine (Mellaril and others), topiramate (Topamax), valproate (Depakote), ziprasidone (Geodon).


  1. 1.

    Cradock-O'Leary J, Young AS, Yano EM, Wang M, Lee ML: Use of general medical services by VA patients with psychiatric disorders. Psychiatric Services. 2002, 53: 874-878. 10.1176/

    Article  PubMed  Google Scholar 

  2. 2.

    McGinnis JM, Foege WH: Actual causes of death in the United States. JAMA. 1993, 270: 2207-2212. 10.1001/jama.270.18.2207.

    CAS  Article  PubMed  Google Scholar 

  3. 3.

    Flegal KM, Carroll MD, Ogden CL, Johnson CL: Prevalence and trends in obesity among US adults, 1999–2000. JAMA. 2002, 288: 1723-1727. 10.1001/jama.288.14.1723.

    Article  PubMed  Google Scholar 

  4. 4.

    Fagiolini A, Kupfer DJ, Houck PR, Novick DM, Frank E: Obesity as a correlate of outcome in patients with bipolar I disorder. Am J Psychiatry. 2003, 160: 112-117. 10.1176/appi.ajp.160.1.112.

    Article  PubMed  Google Scholar 

  5. 5.

    Elmslie JL, Mann JI, Silverstone JT, Williams SM, Romans SE: Determinants of overweight and obesity in patients with bipolar disorder. J Clin Psychiatry. 2001, 62: 486-491.

    CAS  Article  PubMed  Google Scholar 

  6. 6.

    Bavenholm PN, Kuhl J, Pigon J, Saha AK, Ruderman NB, Efendic S: Insulin resistance in type 2 diabetes: association with truncal obesity, impaired fitness, and atypical malonyl coenzyme A regulation. J Clin Endocrinol Metab. 2003, 88: 82-87. 10.1210/jc.2002-020330.

    CAS  Article  PubMed  Google Scholar 

  7. 7.

    Freedman DS, Williamson DF, Croft JB, Ballew C, Byers T: Relation of body fat distribution to ischemic heart disease. The National Health and Nutrition Examination Survey I (NHANES I) epidemiologic follow-up study. Am J Epidemiol. 1995, 142: 53-63.

    CAS  PubMed  Google Scholar 

  8. 8.

    Pi-Synyer FX: Comorbidities of overweight and obesity: current evidence and research issues. Med Sci Sports Exerc. 1999, Suppl 11: S602-608. 10.1097/00005768-199911001-00019.

    Article  Google Scholar 

  9. 9.

    Gohil BC, Resenblum LA, Coplan JD: Hypothalamic-pituitary-adrenal axis function and the metabolic syndrome X of obesity. CNS Spectrums. 2001, 6: 581-589.

    CAS  PubMed  Google Scholar 

  10. 10.

    Elmslie JL, Siverstone JT, Mann JI, Williams SM, Romans MD: Prevalence of overweight and obesity in bipolar patients. J Clin Psychiatry. 2000, 61: 179-184.

    CAS  Article  PubMed  Google Scholar 

  11. 11.

    Baptista T: Body weight gain induced by antipsychotic drugs: mechanisms and management. Acta Psychiatr Scand. 1999, 100: 3-16.

    CAS  Article  PubMed  Google Scholar 

  12. 12.

    Greenberg I, Chan S, Blackburn GL: Nonpharmacologic and pharmacologic management of weight gain. J Clin Psychiatry. 1999, 60 Suppl 21: 31-36.

    CAS  PubMed  Google Scholar 

  13. 13.

    Fontbonne A, Charles MA, Juhan-Vague I, Bard JM, Andre P, Isnard F, Cohen JM, Grandmottet P, Vague P, Safar ME, Eschwege E: The effect of metformin on the metabolic abnormalities associated with upper-body fat distribution. BIGPRO study group. Diabetes Care. 1996, 19: 920-926.

    CAS  Article  PubMed  Google Scholar 

  14. 14.

    Glueck CJ, Fontaine RN, Wang P, Subbiah MT, Weber K, Illig E, Streicher P, Sieve-Smith L, Tracy TM, Lang JE, McCullough P: Metformin reduces weight, centripetal obesity, insulin, leptin, and low-density lipoprotein cholesterol in nondiabetic, morbidly obese subjects with body mass index greater than 30. Metabolism. 2001, 50: 856-861. 10.1053/meta.2001.24192.

    CAS  Article  PubMed  Google Scholar 

  15. 15.

    Morrison JA, Cottingham EM, Barton BA: Metformin for weight loss in pediatric patients taking psychotropic drugs. Am J Psychiatry. 2002, 159: 655-657. 10.1176/appi.ajp.159.4.655.

    Article  PubMed  Google Scholar 

  16. 16.

    Erfurth A, Kuhn G: Topiramate monotherapy in the maintenance treatment of bipolar I disorder: effects on mood, weight and serum lipids. Neuropsychobiology. 2000, Suppl 1: 50-51. 10.1159/000054854.

    Article  Google Scholar 

  17. 17.

    Correa N, Opler LA, Kay SR, Birmaher B: Amantadine in the treatment of neuroendocrine side-effects of neuroleptics. J Clin Psychopharmacol. 1987, 7: 91-95.

    CAS  PubMed  Google Scholar 

  18. 18.

    Floris M, Lejeune J, Deberdt W: Effect of amantadine on weight gain during olanzapine treatment. European Neuropsychopharmacology. 2001, 11: 181-182. 10.1016/S0924-977X(01)00072-4.

    CAS  Article  PubMed  Google Scholar 

  19. 19.

    Sacchetti E, Guarneri L, Bravi D: H2 antagonist nizatidine may control olanzapine-associated weight gain in schizophrenic patients. Biol Psychiatry. 2000, 48: 167-168. 10.1016/S0006-3223(00)00872-6.

    CAS  Article  PubMed  Google Scholar 

  20. 20.

    Anghelescu I, Klawe C, Benkert O: Orlistat in the treatment of psychopharmacologically induced weight gain [letter]. J Clin Psychopharmacol. 2000, 20: 716-717. 10.1097/00004714-200012000-00029.

    CAS  Article  PubMed  Google Scholar 

  21. 21.

    Malhotra S, McElroy SL: Medical management of obesity associated with mental disorders. J Clin Psychiatry. 2002, 63 Suppl 4: 24-32.

    PubMed  Google Scholar 

  22. 22.

    Silver H, Geraisy FN: Amantidine does not exacerbate positive symptoms in medicated, chronic schizophrenic patients: evidence from a double-blind crossover study. J Clin Psychopharmacol. 1997, 16: 463-464. 10.1097/00004714-199612000-00014.

    Article  Google Scholar 

  23. 23.

    Taflinski T, Chojnacka J: Sibutramine-associated psychotic episode [letter]. Am J Psychiatry. 2000, 157: 2056-2057. 10.1176/appi.ajp.157.12.2057-a.

    Article  Google Scholar 

  24. 24.

    Cassidy F, Ahearn E, Carroll BJ: Elevated frequency of diabetes mellitus in hospitalized manic-depressive patients. Am J Psychiatry. 1999, 156: 1417-1420.

    CAS  PubMed  Google Scholar 

  25. 25.

    Yang SH, McNeely MJ: Rhabdomyolysis, pancreatitis, and hyperglycemia with ziprasidone. Am J Psychiatry. 2002, 159: 1435-10.1176/appi.ajp.159.8.1435.

    Article  PubMed  Google Scholar 

  26. 26.

    Lindenmayer JP, Czobor P, Volavka J, Citrome L, Sheitman B, McEvoy JP, Cooper TB, Chakos M, Lieberman JA: Changes in glucose and cholesterol levels in patients with schizophrenia treated with typical or atypical antipsychotics. Am J Psychiatry. 2003, 160: 290-296. 10.1176/appi.ajp.160.2.290.

    Article  PubMed  Google Scholar 

  27. 27.

    Kato MM, Goodnick PJ: Antipsychotic medication: effects on regulation of glucose and lipids. Expert Opin Pharmacother. 2001, 2: 1571-1582.

    CAS  Article  PubMed  Google Scholar 

  28. 28.

    Sowell MO, Mukhopadhyay N, Cavazzoni P, Shankar S, Steinberg HO, Breier A, Beasley CM, Dananberg J: Hyperglycemic clamp assessment of insulin secretory responses in normal subjects treated with olanzapine, risperidone or placebo. J Clin Endocrinol Metab. 2002, 87: 2918-2923. 10.1210/jc.87.6.2918.

    CAS  Article  PubMed  Google Scholar 

  29. 29.

    Luna B, Feinglos MN: Drug-induced hyperglycemia. JAMA. 2001, 286: 1945-1948. 10.1001/jama.286.16.1945.

    CAS  Article  PubMed  Google Scholar 

  30. 30.

    Wirshing DA, Boyd JA, Meng LR, Ballon JS, Marder SR, Wirshing WC: The effects of novel antipsychotics on glucose and lipid levels. J Clin Psychiatry. 2002, 63: 856-865.

    CAS  Article  PubMed  Google Scholar 

  31. 31.

    Osser DN, Najarian DM, Dufresne RL: Olanzapine increases weight and serum triglyceride levels. J Clin Psychiatry. 1999, 60: 767-770.

    CAS  Article  PubMed  Google Scholar 

  32. 32.

    Melkersson KI, Hulting AL, Brismar KE: Elevated levels of insulin, leptin, and blood lipids in olanzapine-treated patients with schizophrenia or related psychoses. J Clin Psychiatry. 2000, 61: 742-9.

    CAS  Article  PubMed  Google Scholar 

  33. 33.

    Kinon BJ, Basson BR, Gilmore JA, Tollefson GD: Long-term olanzapine treatment: weight change and weight-related health factors in schizophrenia. J Clin Psychiatry. 2001, 62: 92-100.

    CAS  Article  PubMed  Google Scholar 

  34. 34.

    Brown DW, Ketter TA, Crumlish J, Post RM: Carbamazepine-induced increases in total serum cholesterol: clinical and theoretical implications. J Clin Psychopharmacol. 1992, 12: 431-437.

    CAS  PubMed  Google Scholar 

  35. 35.

    Isojarvi JI, Pakarinen AJ, Myllyla VV: Serum lipid levels during carbamazepine medication. A prospective study. Arch Neurol. 1993, 50: 590-593.

    CAS  Article  PubMed  Google Scholar 

  36. 36.

    Isojarvi JI, Pakarinen AJ, Rautio A, Pelkonen O, Myllyla VV: Liver enzyme induction and serum lipid levels after replacement of carbamazepine with oxcarbazepine. Epilepsia. 1994, 35: 1217-1220.

    CAS  Article  PubMed  Google Scholar 

  37. 37.

    Isojarvi JI, Tauboll E, Pakarinen AJ, van Parys J, Rattya J, Harbo HF, Dale PO, Fauser BC, Gjerstad L, Koivunen R, Knip M, Tapanainen JS: Altered ovarian function and cardiovascular risk factors in valproate-treated women. Amer J Med. 2001, 111: 290-296. 10.1016/S0002-9343(01)00806-3.

    CAS  Article  PubMed  Google Scholar 

  38. 38.

    Stephen LJ, Kwan P, Shapiro D, Dominiczak M, Brodie MJ: Hormone profiles in young adults with epilepsy treated with sodium valproate or lamotrigine monotherapy. Epilepsia. 2001, 42: 1002-1006. 10.1046/j.1528-1157.2001.0420081002.x.

    CAS  Article  PubMed  Google Scholar 

  39. 39.

    McIntyre RS, Mancini DA, McCann S, Srinivasan J, Kennedy SH: Valproate, bipolar disorder and polycystic ovarian syndrome. Bipolar Disorders. 2003, 5: 28-35. 10.1034/j.1399-5618.2003.00009.x.

    CAS  Article  PubMed  Google Scholar 

  40. 40.

    Sharma R, Markar HR: Mortality in affective disorder. J Affect Disord. 1994, 31: 91-96. 10.1016/0165-0327(94)90112-0.

    CAS  Article  PubMed  Google Scholar 

  41. 41.

    Benowitz NL: Effects of cardiac disease on pharmacokinetics: pathophysiologic considerations. In Pharmacologic Basis for Drug Treatment. Edited by: Benet LZ, Massoud N, Gambertoglio JG. 1984, New York:Raven Press

    Google Scholar 

  42. 42.

    DasGupta K, Jefferson JW: The use of lithium in the medically ill. General Hospital Psychiatry. 1990, 12: 83-97. 10.1016/0163-8343(90)90019-9.

    CAS  Article  PubMed  Google Scholar 

  43. 43.

    Carruthers SG: Adverse effects of alpha 1-andrenergic blocking drugs. Drug Saf. 1994, 11: 12-20.

    CAS  Article  PubMed  Google Scholar 

  44. 44.

    Marangell LB, Martinez JM, Silver JM, Yudofsky SC: Concise Guide to Psychopharmacology. 2002, Washington, D.C.: American Psychiatric Press

    Google Scholar 

  45. 45.

    Kasarskis EJ, Kuo CS, Berger R, Nelson KR: Carbamazepine-induced cardiac dysfunction. Characterization of two distinct clinical syndromes. Arch Intern Med. 1992, 152: 186-191. 10.1001/archinte.152.1.186.

    CAS  Article  PubMed  Google Scholar 

  46. 46.

    Chong SA, Mythily , Mahendran R: Cardiac effects of psychotropic drugs. Ann Acad Med Singapore. 2001, 30: 625-631.

    CAS  PubMed  Google Scholar 

  47. 47.

    Glassman AH, Bigger JT: Antipsychotic drugs: prolonged QTc interval, torsade de pointes, and sudden death. Am J Psychiatry. 2001, 158: 1774-1782. 10.1176/appi.ajp.158.11.1774.

    CAS  Article  PubMed  Google Scholar 

  48. 48.

    Ravin DS, Levenson JW: Fatal cardiac event following initiation of risperidone therapy. Ann Pharmacother. 1997, 31: 867-70.

    CAS  PubMed  Google Scholar 

  49. 49.

    Piepho RW: Cardiovascular effects of antipsychotics used in bipolar illness. J Clin Psychiatry. 2002, 63 Suppl 4: 20-23.

    PubMed  Google Scholar 

  50. 50.

    Taylor DM: Antipsychotics and QT prolongation. Acta Psychiatr Scan. 2003, 107: 85-95. 10.1034/j.1600-0447.2003.02078.x.

    CAS  Article  Google Scholar 

  51. 51.

    Dewan NA, Suresh DP, Blomkalns A: Selecting safe psychotropics for post-MI patients. Current Psychiatry. 2003, 2: 14-21.

    Google Scholar 

  52. 52.

    Leipzig RM: Psychopharmacology in patients with hepatic and gastrointestinal disease. Int J Psychiatry Med. 1990, 20: 109-139.

    CAS  Article  PubMed  Google Scholar 

  53. 53.

    Seeff LB, Hoofnagle JH: Appendix: The National Institutes of Health consensus development conferences management of hepatitis C 2002. Clin Liver Dis. 2003, 7: 261-287.

    Article  PubMed  Google Scholar 

  54. 54.

    El-Serag HB, Kunik M, Richardson P, Rabeneck L: Psychiatric disorders among veterans with hepatitis C infection. Gastroenterology. 2002, 123: 476-482. 10.1053/gast.2002.34750.

    Article  PubMed  Google Scholar 

  55. 55.

    Felker BL, Sloan KL, Dominitz JA, Barnes RF: The safety of valproic acid use for patients with hepatitis C infection. Am J Psychiatry. 2003, 160: 174-178. 10.1176/appi.ajp.160.1.174.

    Article  PubMed  Google Scholar 

  56. 56.

    Bryant AE, Dreifuss FE: Valproic acid hepatic fatalities. III. U.S. experience since 1986. Neurology. 1996, 46: 465-469.

    Article  PubMed  Google Scholar 

  57. 57.

    Chitturi S, George J: Hepatotoxicity of commonly used drugs: nonsteroidal anti-inflammatory drugs, antihypertensives, antidiabetic agents, anticonvulsants, lipid-lowering agents, psychotropic drugs. Semin Liver Dis. 2002, 22: 169-183. 10.1055/s-2002-30102.

    CAS  Article  PubMed  Google Scholar 

  58. 58.

    Vittorio C, Muglia J: Anticonvulsant hypersensitivity syndrome. Arch Intern Med. 1995, 155: 2285-2290. 10.1001/archinte.155.21.2285.

    CAS  Article  PubMed  Google Scholar 

  59. 59.

    Overstreet K, Costanza C, Behling C, Hassanin T, Masliah E: Fatal progressive hepatic necrosis associated with lamotrigine treatment: a case report and literature review. Dig Dis Sci. 2002, 47: 1921-1925. 10.1023/A:1019627618972.

    Article  PubMed  Google Scholar 

  60. 60.

    Snoeck E, Van Peer A, Sack M, Horton M, Mannens G, Woestenborghs R, Meibach R, Heykants J: Influence of age, renal, and liver impairment on the pharmacokinetics of risperidone in man. Psychopharmacology. 1995, 122: 223-229.

    CAS  Article  PubMed  Google Scholar 

  61. 61.

    DeVane CL, Nemeroff CB: Clinical pharmacokinetics of quetiapine: an atypical antipsychotic. Clin Pharmacokinet. 2001, 40: 509-522.

    CAS  Article  PubMed  Google Scholar 

  62. 62.

    Thyrum PT, Wong YW, Yeh C: Single-dose pharmacokinetics of quetiapine in subjects with renal or hepatic impairment. Prog Neuropsychopharmacol Biol Psychiatry. 2000, 24: 521-533. 10.1016/S0278-5846(00)00090-7.

    CAS  Article  PubMed  Google Scholar 

  63. 63.

    Swann AC: Major system toxicities and side effects of anticonvulsants. J Clin Psychiatry. 2001, 62 Suppl 14: 16-21.

    CAS  PubMed  Google Scholar 

  64. 64.

    Coresh J, Astor BC, Greene T, Eknoyan G, Levey AS: Prevalence of chronic kidney disease and decreased kidney function in the adult US population: third national health and nutrition examination survey. Am J Kidney Dis. 2003, 41: 1-12. 10.1053/ajkd.2003.50007.

    Article  PubMed  Google Scholar 

  65. 65.

    Arias E, Smith BL: Deaths: preliminary data for 2001. Natl Vital Stat Rep. 2003, 51: 1-44.

    Google Scholar 

  66. 66.

    Hestbach J, Hansen HE, Amdisen A: Chronic renal lesions following long-term treatment with lithium. Kidney Int. 1977, 12: 205-213.

    Article  Google Scholar 

  67. 67.

    Wood IK, Parmelee DX, Foreman JW: Lithium-induced nephrotic syndrome. Am J Psychiatry. 1989, 146: 84-87.

    CAS  Article  PubMed  Google Scholar 

  68. 68.

    Flynn CT, Chandran PKG, Taylor MJ, Shadur CA: Intraperitoneal lithium administration for bipolar affective disorder in a patient on continuous ambulatory peritoneal dialysis. Int J Artif Organs. 1987, 10: 105-107.

    CAS  PubMed  Google Scholar 

  69. 69.

    Koecheler JA, Canafax DM, Simmons RL, Najarian JS: Lithium dosing in renal allograft recipients with changing renal runction. Drug Intell Clin Pharm. 1986, 20: 623-624.

    CAS  PubMed  Google Scholar 

  70. 70.

    Potter JM, Donnelly A: Carbamazepine-10,11-epoxide in therapeutic drug monitoring. Ther Drug Monit. 1998, 20: 652-657. 10.1097/00007691-199812000-00012.

    CAS  Article  PubMed  Google Scholar 

  71. 71.

    Abbott Laboratories: Depakote, package insert. North Chicago, IL. 1997

    Google Scholar 

  72. 72.

    Wootton R, Soul-Lawton J, Rolan PE, Sheung CT, Cooper JD, Posner J: Comparison of the pharmacokinetics of lamotrigine in patients with chronic renal failure and healthy volunteers. Br J Clin Pharmacol. 1997, 43: 23-27.

    CAS  Article  PubMed  Google Scholar 

  73. 73.

    Fillastre JP, Taburet AM, Fialaire A, Etienne I, Bidault R, Singlas E: Pharmacokinetics of lamotrigine in patients with renal impairment: influence of haemodialysis. Drugs Exp Clin Res. 1993, 19: 25-32.

    CAS  PubMed  Google Scholar 

  74. 74.

    McLean MJ: Clinical pharmacokinetics of gabapentin. Neurology. 1994, 44 Suppl 5: S17-22.

    Google Scholar 

  75. 75.

    Rosenfeld WE: Topiramate: a review of preclinical, pharmacokinetic, and clinical data. Clin Therapeutics. 1997, 19: 1294-1308. 10.1016/S0149-2918(97)80006-9.

    CAS  Article  Google Scholar 

  76. 76.

    Ereshefsky L: Pharmacokinetics and drug interactions: update for new antipsychotics. J Clin Psychiatry. 1996, 57 Suppl 11: 12-25.

    CAS  PubMed  Google Scholar 

  77. 77.

    Aweeka F, Jayesekara D, Horton M, Swan S, Lambrecht L, Wilner KD, Sherwood J, Anxiano RJ, Smolarek TA, Turncliff RZ: The pharmacokinetics of ziprasidone in subjects with normal and impaired renal function. Br J Clin Pharmacol. 2000, Suppl 1: 27S-33S. 10.1046/j.1365-2125.2000.00150.x.

    Google Scholar 

  78. 78.

    Physicians' Desk Reference: Geodon for injection. Thompson PDR. 2004, 2597-2603.

    Google Scholar 

  79. 79.

    Mouallem M, Wolf I: Olanzapine-induced respiratory failure. Am J Geriatr Psychiatry. 2001, 9: 304-305. 10.1176/appi.ajgp.9.3.304.

    CAS  Article  PubMed  Google Scholar 

  80. 80.

    Shelton PS, Barnett FL, Krick SE: Hyperventilation associated with quetiapine. Ann of Pharmacotherapy. 2000, 34: 335-337. 10.1345/aph.19232.

    CAS  Article  Google Scholar 

  81. 81.

    Lerner DM, Schuetz L, Holland S, Rubinow DR, Rosenstein DL: Low-dose risperidone for the irritable medically ill patient. Psychosomatics. 2000, 41: 69-71.

    CAS  Article  PubMed  Google Scholar 

  82. 82.

    Passik SD, Lundberg J, Kirsh KL, Theobald D, Donaghy K, Holtsclaw E, Cooper M, Dugan W: A pilot exploration of the antiemetic activity of olanzapine for the relief of nausea in patients with advanced cancer and pain. J Pain Symptom Manage. 2002, 23: 526-532. 10.1016/S0885-3924(02)00391-3.

    CAS  Article  PubMed  Google Scholar 

  83. 83.

    Khojainova N, Santiago-Palma J, Kornick C, Breitbart W, Gonzales GR: Olanzapine in the management of cancer pain. J Pain Symptom Manage. 2002, 23: 346-350. 10.1016/S0885-3924(02)00378-0.

    CAS  Article  PubMed  Google Scholar 

Download references

Author information



Corresponding author

Correspondence to Lauren B Marangell.

Additional information

Competing interests

KM has declared no competing interests. LM receives grant/research support from the National Institute of Health (NIH), the Stanley Medical Research Institute, Cyberonics, Eli Lilly and Company and Abbott Laboratories; acts as a consultant to Bristol-Myers Squibb, Cyberonics, Eli Lilly and Company, Forest Laboratories, GlaxoSmithKline, Janssen, Novartis and Wyeth Pharmaceuticals; and has received honoraria from AstraZeneca, Bristol-Myers Squibb, Cyberonics, Eli Lilly and Company, Forest Laboratories, GlaxoSmithKline, Pfizer Inc., and Wyeth Pharmaceuticals.

Authors' contributions

KM reviewed the literature and drafted the manuscript. LM identified the need for this review paper, participated in drafting the manuscript, and presented the findings, in part, at the American Psychiatric Association annual meeting in San Francisco, CA on May 18, 2003. Both authors read and approved the final manuscript.

Rights and permissions

Reprints and Permissions

About this article

Cite this article

McLaren, K.D., Marangell, L.B. Special considerations in the treatment of patients with bipolar disorder and medical co-morbidities. Ann Gen Hosp Psychiatry 3, 7 (2004).

Download citation


  • bipolar disorder
  • medical illness
  • obesity
  • diabetes mellitus
  • dyslipidemia
  • cardiac disease
  • hepatic disease
  • renal disease
  • pulmonary disease
  • cancer
  • mood stabilizers
  • anticonvulsants
  • atypical antipsychotics