Fluoxetine / olanzapine Side Effects

Not all side effects for fluoxetine / olanzapine may be reported. You should always consult a doctor or healthcare professional for medical advice. Side effects can be reported to the FDA here.

For the Consumer

Applies to fluoxetine / olanzapine: oral capsule

In addition to its needed effects, some unwanted effects may be caused by fluoxetine / olanzapine. In the event that any of these side effects do occur, they may require medical attention.

You should check with your doctor immediately if any of these side effects occur when taking fluoxetine / olanzapine:

More common
  • Bloating or swelling of the face, arms, hands, lower legs, or feet
  • body aches or pain
  • confusion
  • congestion
  • cough
  • delusions
  • dementia
  • dryness or soreness of the throat
  • fever
  • hoarseness
  • rapid weight gain
  • runny nose
  • shakiness in the legs, arms, hands, or feet
  • tender, swollen glands in the neck
  • tingling of the hands or feet
  • trembling or shaking of the hands or feet
  • trouble with swallowing
  • unusual weight gain or loss
  • voice changes
Less common
  • Blurred vision
  • change in personality
  • change in vision
  • difficult or labored breathing
  • difficulty with sleeping
  • difficulty with speaking
  • dizziness
  • ear pain
  • headache
  • impaired vision
  • increase in body movements
  • loss of memory
  • nervousness
  • pounding in the ears
  • problems with memory
  • slow, fast, pounding, or irregular heartbeat or pulse
  • tightness in the chest
Rare
  • Inability to move the eyes
  • increased blinking or spasms of the eyelid
  • sticking out of the tongue
  • uncontrolled twisting movements of the neck, trunk, arms, or legs
  • unusual facial expressions
Incidence not known
  • Bloody or black, tarry stools
  • constipation
  • severe stomach pain
  • vomiting of blood or material that looks like coffee grounds

Some of the side effects that can occur with fluoxetine / olanzapine may not need medical attention. As your body adjusts to the medicine during treatment these side effects may go away. Your health care professional may also be able to tell you about ways to reduce or prevent some of these side effects. If any of the following side effects continue, are bothersome or if you have any questions about them, check with your health care professional:

More common
  • Diarrhea
  • dry mouth
  • increased appetite
  • lack or loss of strength
  • weight gain
Less common
  • Change or problem with discharge of semen
  • decreased interest in sexual intercourse
  • difficulty with moving
  • inability to have or keep an erection
  • loss in sexual ability, desire, drive, or performance
  • muscle pain or stiffness
  • not able to have an orgasm
  • pain, swelling, or redness in the joints
  • tooth disorder
  • twitching

For Healthcare Professionals

Applies to fluoxetine / olanzapine: oral capsule

General

Commonly reported side effects associated with fluoxetine-olanzapine treatment in short-term controlled studies at an incidence of at least 5% and double that of placebo were disturbance in attention, dry mouth, fatigue, hypersomnia, increased appetite, peripheral edema, sedation, somnolence, tremor, blurred vision, and increased weight.

Statistically significant differences in the incidence of weight gain, prolactin elevation, fatigue, and dizziness have been observed in a single 8-week randomized, double-blind, fixed dose study comparing 10 mg, 20 mg, and 40 mg olanzapine in patients with schizophrenia or schizoaffective disorder. Side effects associated with treatment discontinuation were increased weight and sedation.

In a single, 8-week, randomized, placebo-controlled clinical trial of fluoxetine-olanzapine for the treatment of bipolar I depression in patients aged 10 to 17 years, the side effects that lead to discontinuation that occurred at an incidence of at least 1% and greater than that of the placebo group were increased weight, suicidal ideation, bipolar disorder, and somnolence.[Ref]

Psychiatric

Antidepressants may have a role in inducing worsening of depression and the emergence of suicidality in certain patients during the early phases of treatment. An increased risk of suicidal thinking and behavior in children, adolescents, and young adults (aged 18 to 24 years) with major depressive disorder (MDD) and other psychiatric disorders has been reported with short-term use of antidepressant drugs.

Adult and pediatric patients receiving antidepressants for MDD, as well as for psychiatric and nonpsychiatric indications, have reported symptoms that may be precursors to emerging suicidality, including anxiety, agitation, panic attacks, insomnia, irritability, hostility, aggressiveness, impulsivity, akathisia, hypomania, and mania. Causality has not been established.

Placebo-controlled clinical trials in elderly patients with dementia-related psychosis showed a significantly increased risk of death in olanzapine-treated patients (3.5%) compared to placebo-treated patients (1.5%).

Somnolence, anxiety, restlessness, and suicidal ideation were reported as a treatment-emergent side effect in an 8-week randomized, double-blind, placebo-controlled clinical trial in pediatric bipolar I depression in patients aged 10 to 17 years.[Ref]

Very common (10% or more): Somnolence
Common (1% to 10%): Disturbance in attention, nervousness, restlessness, thinking abnormal
Uncommon (0.1% to 1%): Depersonalization, dysarthria, emotional lability, euphoria
Frequency not reported: Violent behaviors[Ref]

Nervous system

Common (1% to 10%): Tremor
Uncommon (0.1% to 1%): Ataxia, coma, hypokinesia, movement disorder, myoclonus
Rare (less than 0.1%): Hyperkinesia
Frequency not reported: Dystonias, headache[Ref]

Dystonias may occur in the first few days of treatment; males and younger age groups appear to be at a greater risk for acute dystonia. The frequency and severity of symptoms appear greater with high potency and at higher doses of first generation antipsychotic drugs, but may occur at low doses.

One retrospective study of 23 outpatients with Parkinson's disease treated with 40 mg of fluoxetine a day reported that three patients experienced worsening of parkinsonism, two patients experienced improvement of parkinsonism, and 18 patients experienced no change. Another small study reported a series of four patients who experienced worsening of parkinsonism during treatment with fluoxetine.

A number of case reports have implicated fluoxetine in causing seizures. Twelve of 6000 patients experienced convulsions during pre-marketing testing.

A case of dose-dependent exacerbation of preexisting, mild restless legs syndrome (which ultimately required discontinuation of fluoxetine) has been reported.

Tremor was reported as a treatment-emergent side effect in an 8-week randomized, double-blind, placebo-controlled clinical trial in pediatric bipolar I depression in patients aged 10 to 17 years.[Ref]

Metabolic

Numerous cases of hyponatremia have been reported following treatment with an SSRI. Risk factors for the development of SSRI- associated hyponatremia including advanced age, female gender, concomitant use of diuretics, low body weight, and lower baseline serum sodium levels have been identified. Hyponatremia tends to develop within the first few weeks of treatment (range 3 to 120 days) and typically resolves within 2 weeks (range 48 hours to 6 weeks) after therapy has been discontinued with some patients requiring treatment. The proposed mechanism for the development of hyponatremia involves SIADH via release of antidiuretic hormone.

Hyperglycemia has been reported with olanzapine alone as well as in combination with fluoxetine. In an analysis of 7 controlled clinical studies, 2 of which were placebo controlled, with treatment duration up to 12 weeks, fluoxetine-olanzapine was associated with a greater mean change in random glucose compared to placebo (+8.65 mg/dL versus -3.86 mg/dL). The difference in mean changes was greater in patients with evidence of glucose dysregulation at baseline. Epidemiological studies suggest an increased risk of treatment-emergent hyperglycemia in patients treated with atypical antipsychotics. The association between atypical antipsychotic therapy and increases in glucose levels appears greater with olanzapine than some other atypical antipsychotic agents.

Elevated uric acid, low albumin, low bicarbonate, and low inorganic phosphorus were observed at a statistically significant greater frequency in the fluoxetine-olanzapine group compared to the placebo group in adult clinical studies. Clinically meaningful increases in total cholesterol and triglyceride levels, sometimes greater than 500 mg/dL have also been observed in adults.

Clinically significant weight gain across all baseline BMI categories has been reported in clinical trials with fluoxetine-olanzapine. An analysis of 7 controlled clinical studies (2 of which were placebo-controlled) reported that, after a median exposure of eight weeks, 22% of patients treated with fluoxetine-olanzapine had gained at least 7% of their baseline weight. Long-term studies with fluoxetine-olanzapine (n=431), where patients were treated with this combination for at least 48 weeks, showed a mean weight gain of 6.7 kg.

Increased weight, appetite, blood triglycerides, and cholesterol were reported as treatment-emergent side effects in an 8 week randomized, double-blind, placebo-controlled clinical trial in pediatric bipolar I depression in patients aged 10 to 17 years. High fasting total cholesterol, high fasting LDL cholesterol, and high fasting triglycerides were observed at statistically significant greater frequencies in the fluoxetine-olanzapine group compared to the placebo group.[Ref]

Very common (10% or more): High fasting LDL cholesterol, high fasting triglycerides, high fasting total cholesterol, low bicarbonate, increased appetite, increased weight
Common (1% to 10%): Elevated uric acid, low albumin, low inorganic phosphorus, weight loss
Rare (less than 0.1%): Gout
Frequency not reported: Hyperglycemia, increased creatine phosphokinase, random triglyceride levels of 1000 mg/dL or more[Ref]

Cardiovascular

The mean standing pulse rate in patients treated with fluoxetine-olanzapine was reduced by 0.7 beats/minute.

QTcF interval prolongation of 450 milliseconds or more for males and 470 milliseconds for females was reported at an incidence of at least 1% in clinical trials. The mean increase in QTc interval was reported as significantly greater in fluoxetine-olanzapine treated patients than placebo-treated patients, olanzapine-treated, and fluoxetine-treated patients.

Mean increases in QTcF interval of 8.2 milliseconds was observed at a statistically significant greater frequency in the fluoxetine-olanzapine group compared to the placebo group in a single 8-week randomized, placebo-controlled clinical trial for bipolar I depression in children and adolescents aged 10 to 17 years.

One placebo-controlled study has suggested that fluoxetine has no effects on intraventricular conduction. Other case reports have suggested that fluoxetine may rarely provoke dysrhythmias. Other conflicting case reports have suggested that fluoxetine may have a propensity to provoke and alleviate vasoconstriction. Several cases of unexpected death occurring shortly after initiation of fluoxetine therapy have been reported in elderly patients with multiple medical problems.

In one case report, QTc prolongation and torsades de pointes developed in an elderly woman 6 months after starting therapy with fluoxetine 20 mg daily. The QTc interval returned to normal following discontinuation of fluoxetine. Four additional cases suggesting fluoxetine-associated QTc prolongation or torsades de pointes have been reported.[Ref]

Very common (10% or more): Edema
Common (1% to 10%): Generalized edema, vasodilatation
Frequency not reported: Bradycardia, hypotension, orthostatic hypotension, tachycardia
Postmarketing reports: Deep vein thrombosis[Ref]

Other

Potentially life-threatening serotonin syndrome has been reported with SSRIs and SNRIs as monotherapy, but particularly with concomitant use of other serotonergic drugs and drugs that impair the metabolism of serotonin.

Accidental overdose was reported as a treatment-emergent side effect in an 8-week randomized, double-blind, placebo-controlled clinical trial in pediatric bipolar I depression in patients aged 10 to 17 years.

Neuroleptic Malignant Syndrome (NMS), a potentially fatal symptom complex, has been reported in connection to treatment with antipsychotic drugs, including olanzapine.[Ref]

Very common (10% or more): Fatigue
Common (1% to 10%): Asthenia, chills, neck rigidity, pain, pyrexia
Rare (less than 0.1%): Death, withdrawal syndrome
Frequency not reported: Body temperature dysregulation[Ref]

Genitourinary

Common (1% to 10%): Breast pain, erectile dysfunction, menorrhagia, urinary frequency, urinary incontinence
Uncommon (0.1% to 1%): Amenorrhea, female lactation, hypomenorrhea, metrorrhagia, urinary retention, urinary urgency, impaired urination
Rare (less than 0.1%): Breast engorgement, increased libido
Frequency not reported: Abnormal ejaculation, anorgasmia, decreased libido, dysuria, gynecological bleeding[Ref]

Urinary retention and galactorrhea have been reported with other SSRIs.

The estimates of the incidence of untoward sexual experience and performance may underestimate their actual incidence, partly because patients and physicians may be reluctant to discuss this issue. In placebo-controlled clinical trials ejaculation disorder (primarily ejaculation delay) was reported as a treatment-emergent side effect at an incidence of 6% and at least twice the incidence in placebo-treated male patients.

Dysmenorrhea was reported as a treatment-emergent side effect in an 8-week randomized, double-blind, placebo-controlled clinical trial in pediatric bipolar I depression in patients aged 10 to 17 years.[Ref]

Dermatologic

Common (1% to 10%): Ecchymosis
Uncommon (0.1% to 1%): Alopecia, dry skin, pruritus
Rare (less than 0.1%): Exfoliative dermatitis, purpura
Frequency not reported: Erythema multiforme, sweating[Ref]

Approximately 3% of fluoxetine-treated patients have been reported to develop a skin reaction.[Ref]

Endocrine

Very common (10% or more): Elevated prolactin
Frequency not reported: Diabetic coma[Ref]

Elevated prolactin levels were observed at a statistically significant greater frequency in the fluoxetine-olanzapine group compared to the placebo group in adult clinical studies and also in a single 8-week randomized, placebo-controlled clinical trial for bipolar I depression in children and adolescents aged 10 to 17 years.[Ref]

Gastrointestinal

A study of 26,005 antidepressant users has reported 3.6 times more upper GI bleeding episodes with the use of SSRIs relative to the population who did not receive antidepressant medications. Upper gastrointestinal tract bleeding was observed in 3.9 times more frequently in patients receiving fluoxetine.

Dyspepsia was reported as a treatment-emergent side effect in an 8-week randomized, double-blind, placebo-controlled clinical trial in pediatric bipolar I depression in patients aged 10 to 17 years.[Ref]

Very common (10% or more): Dry mouth
Common (1% to 10%): Abdominal distension, diarrhea, flatulence, taste perversion
Uncommon (0.1% to 1%): Buccoglossal syndrome, gastritis, gastroenteritis, nausea and vomiting, peptic ulcer
Rare (less than 0.1%): Gastrointestinal hemorrhage, intestinal obstruction, pancreatitis
Frequency not reported: Bruxism, esophageal ulcer[Ref]

Hematologic

Common (1% to 10%): Low hemoglobin, low lymphocytes
Uncommon (0.1% to 1%): Anemia, thrombocytopenia
Rare (less than 0.1%): Leukopenia
Frequency not reported: Aplastic anemia, neutropenia[Ref]

Low lymphocytes and low hemoglobin were observed at a statistically significant greater frequency in the fluoxetine-olanzapine group compared to the placebo group in adult clinical studies[Ref]

Hepatic

ALT levels reported to return to normal, or were decreasing, at last follow-up in the majority of patients who either continued or discontinued treatment with fluoxetine-olanzapine.

Low total bilirubin levels were observed at a statistically significant greater frequency in the fluoxetine-olanzapine group compared to the placebo group in adult clinical studies. Elevated ALT and AST levels were observed at statistically significant greater frequencies in the fluoxetine-olanzapine group compared to the placebo group in a single 8-week randomized, placebo-controlled clinical trial for bipolar I depression in children and adolescents aged 10 to 17 years.[Ref]

Very common (10% or more): Elevated ALT and AST, low total bilirubin
Common (1% to 10%): Clinically significant ALT elevation less than 3 times the upper limit of normal (ULN), ALT elevations 5 times the ULN or more.
Rare (less than 0.1%): Bilirubinemia , liver fatty deposit
Frequency not reported: Cholestatic jaundice, increased alkaline phosphatase, jaundice
Postmarketing reports: Cholestatic or mixed liver injury, hepatitis[Ref]

Hypersensitivity

Common (1% to 10%): Photosensitivity reaction[Ref]

Musculoskeletal

Common (1% to 10%): Arthralgia, musculoskeletal stiffness, pain in extremity
Rare (less than 0.1%): Osteoporosis
Postmarketing reports: Rhabdomyolysis[Ref]

Epidemiological studies, primarily in patients aged 50 years or older, have shown an increased risk of bone fractures in patients receiving SSRIs or TCAs.

Back pain was reported as a treatment-emergent side effect in an 8-week randomized, double-blind, placebo-controlled clinical trial in pediatric bipolar I depression in patients aged 10 to 17 years.[Ref]

Ocular

Common (1% to 10%): Eye disorders
Uncommon (0.1% to 1%): Abnormality of accommodation, dry eyes[Ref]

Renal

Elevated urea nitrogen levels were observed at a statistically significant greater frequency in the fluoxetine-olanzapine group compared to the placebo group in adult clinical studies.

Glycosuria was reported at an incidence of 4.4% of patients treated with fluoxetine-olanzapine in an analysis of 6 controlled clinical studies, compared to 1.4% in the placebo group.[Ref]

Common (1% to 10%): Elevated urea nitrogen, glycosuria
Rare (less than 0.1%): Increased creatinine[Ref]

Respiratory

Common (1% to 10%): Sinusitis
Uncommon (0.1% to 1%): Epistaxis, yawn
Rare (less than 0.1%): Laryngismus
Frequency not reported: Eosinophilic pneumonia
Postmarketing reports: Pulmonary embolism[Ref]

References

1. "Product Information. Symbyax (fluoxetine-olanzapine)." Lilly, Eli and Company, Indianapolis, IN.

2. "Product Information. Zyprexa (olanzapine)." Lilly, Eli and Company, Indianapolis, IN.

3. "Product Information. Prozac (fluoxetine)." Dista Products Company, Indianapolis, IN.

4. Mann JJ, Kapur S "The emergence of suicidal ideation and behavior during antidepressant pharmacotherapy]." Arch Gen Psychiatry 48 (1991): 1027-33

5. Caley CF, Friedman JH "Does fluoxetine exacerbate Parkinson's disease?" J Clin Psychiatry 53 (1992): 278-82

6. Steur EN "Increase of Parkinson disability after fluoxetine medication." Neurology 43 (1993): 211-3

7. Vishwanath BM, Navalgund AA, Cusano W, Navalgund KA "Fluoxetine as a cause of SIADH." Am J Psychiatry 148 (1991): 542-3

8. Spigset O, hedenmalm K "Hyponatremia in relation to treatment with antidepressants: a survey of reports in the World Health Organization data base for spontaneous reporting of adverse drug reactions." Pharmacotherapy 17 (1997): 348-52

9. Jacob S, Spinler SA "Hyponatremia associated with selective serotonin-reuptake inhibitors in older adults." Ann Pharmacother 40 (2006): 1618-22

10. Schattner A, Skurnik Y "Fluoxetine-induced SIADH." J Am Geriatr Soc 44 (1996): 1413

11. FDA. U.S. Food and Drug Admiinistration. Center for Drug Evaluation and Research "FDA Public Health Advisory. Deaths and antipsychotics in elderly patients with behavioral disturbances. Available from: URL: http://www.fda.gov/cder/drug/advisory/antipsychotics.htm." ([2005 Apr 11]):

12. Wilting I, Smals OM, Holwerda NJ, Meyboom RH, De Bruin ML, Egberts TC "QTc prolongation and torsades de pointes in an elderly woman taking fluoxetine." Am J Psychiatry 163 (2006): 325

13. Herman JB, Brotman AW, Pollack MH, Falk WE, Biederman J, Rosenbaum JF "Fluoxetine-induced sexual dysfunction." J Clin Psychiatry 51 (1990): 25-7

14. Patterson WM "Fluoxetine-induced sexual dysfunction." J Clin Psychiatry 54 (1993): 71

15. Olfson M, Wilner MT "A family case history of fluoxetine-induced skin reactions." J Nerv Ment Dis 179 (1991): 504-5

16. deAbajo FJ, Rodriguez LAG, Montero D "Association between selective serotonin reuptake inhibitors and upper gastrointestinal bleeding: population based case-control study." Br Med J 319 (1999): 1106-9

17. Po AL "Antidepressants and upper gastrointestiinal bleeding: new results suggest a link." BMJ 319 (1999): 1081-2

18. Dalton SO, Johansen C, Mellemkjaer L, Norgard B, Sorensen HT, Olsen JH "Use of selective serotonin reuptake inhibitors and risk of upper gastrointestinal tract bleeding: a population-based cohort study." Arch Intern Med 163 (2003): 59-64

19. Aranth J, Lindberg C "Bleeding, a side effect of fluoxetine." Am J Psychiatry 149 (1992): 412

20. Alderman CP, Moritz CK, Ben-Tovim DI "Abnormal platelet aggregation associated with fluoxetine therapy." Ann Pharmacother 26 (1992): 1517-9

21. Cai Q, Benson MA, Talbot TJ, Devadas G, Swanson HJ, Olson JL, Kirchner JP "Acute hepatitis due to fluoxetine therapy." Mayo Clin Proc 74 (1999): 692-4

22. Liu B, Anderson G, Mittmann N, To Teresa, Axcell T, Shear N "Use of selective serotonin-reuptake inhibitors or tricyclic antidepressants and risk of hip fractures in elderly people." Lancet 351 (1998): 1303-7

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