Symbyax Side Effects
Generic Name: fluoxetine / olanzapine
Note: This page contains side effects data for the generic drug fluoxetine / olanzapine. It is possible that some of the dosage forms included below may not apply to the brand name Symbyax.
It is possible that some side effects of Symbyax may not have been reported. These can be reported to the FDA here. Always consult a healthcare professional for medical advice.
For the Consumer
Applies to fluoxetine / olanzapine: oral capsule
As well as its needed effects, fluoxetine / olanzapine may cause unwanted side effects that require medical attention.
If any of the following side effects occur while taking fluoxetine / olanzapine, check with your doctor immediately:More common
- Bloating or swelling of the face, arms, hands, lower legs, or feet
- body aches or pain
- dryness or soreness of the throat
- 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
- Blurred vision
- change in personality
- change in vision
- difficult or labored breathing
- difficulty with sleeping
- difficulty with speaking
- ear pain
- impaired vision
- increase in body movements
- loss of memory
- pounding in the ears
- problems with memory
- slow, fast, pounding, or irregular heartbeat or pulse
- tightness in the chest
- 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
- Bloody or black, tarry stools
- severe stomach pain
- vomiting of blood or material that looks like coffee grounds
Some fluoxetine / olanzapine side effects may not need any medical attention. As your body gets used to the medicine these side effects may disappear. Your health care professional may be able to help you prevent or reduce these side effects, but do check with them if any of the following side effects continue, or if you are concerned about them:More common
- dry mouth
- increased appetite
- lack or loss of strength
- weight gain
- 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
For Healthcare Professionals
Applies to fluoxetine / olanzapine: oral capsule
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]
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%).
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]
Common (1% to 10%): Nervousness, restlessness, thinking abnormal
Uncommon (0.1% to 1%): Depersonalization, emotional lability, euphoria
Rare (less than 0.1%): Withdrawal syndrome
Frequency not reported: Bruxism, violent behaviors[Ref]
Very common (10% or more): Somnolence
Common (1% to 10%): Disturbance in attention, taste perversion, tremor
Uncommon (0.1% to 1%): Ataxia, coma, dysarthria, 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.
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.
Neuroleptic Malignant Syndrome (NMS), a potentially fatal symptom complex, has been reported in connection to treatment with antipsychotic drugs, including olanzapine.
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.
Somnolence and tremor 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]
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]
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]
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.[Ref]
Very common (10% or more): Fatigue
Common (1% to 10%): Asthenia, chills, neck rigidity, pain, pyrexia
Rare (less than 0.1%): Death
Frequency not reported: Body temperature dysregulation[Ref]
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]
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]
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]
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
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: Esophageal ulcer[Ref]
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]
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]
Common (1% to 10%): Photosensitivity reaction[Ref]
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]
Common (1% to 10%): Eye disorders
Uncommon (0.1% to 1%): Abnormality of accommodation, dry eyes[Ref]
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]
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]
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