TABLE 91-7 -Cardiac-Related Side Effects of Psychotropic Agents Commonly Utilized for Treatment of Anxiety or Depression

Cardiac-Related Side Effects of Psychotropic Agents Commonly Utilized for Treatment of Anxiety or Depression

Class Cardiovascular Side Effect Likely Mechanism of Side Effect Other Effect and Benefits
Tricyclic and related cyclic antidepressants Orthostatic hypotension Postsynaptic alpha1 receptor blockade  
Nortriptyline (Pamelor)     Nortriptyline with lowest incidence of orthostatic hypotension
Imipramine (Tofranil)      
Amitriptyline (Elavil)      
Desipramine (Norpramin) Tachycardia Secouadry to hypotension  
Clomipramine (Anafranil)      
Doxepin (Sinequan) Decreased heart rate variability Postsynaptic cholinergic receptor blockade Urinary retention, dry mouth, constipation, confusion, exacerbation of narrow-angle glaucoma
Trimipramine (Surmontil)      
Protriptyline (Vivactil) Slowing of intraventricular conduction Quinidine-like effects Avoid in patients with bifascicular block, left bundle branch block, QTc > 44 ms, or QRS > 11 ms
Monoamine oxidase inhibitors Orthostatic hypotension Inhibition of metabolism of serotonin and catecholamines Fatal in overdose
Phenelzine (Nardil) Hypertensive crisis   Requires adherence to tyramine-free diet, and avoidance of other antidepressants, and sympathomimetics
Tranylcypromine (Parnate)      
Isocarboxazid (Marplan)      
Selective serotonin reuptake inhibitors (SSRIs)   Postsnaptic serotonin receptor blockade Fatal in overdose
      Typical SSRI side effects: nausea, insomnia, sexual dysfunction, nervousness
Fluoxetine (Prozac) Sinus bradycadia Unknown Requires 8 weeks for complete washout
      Inhibator of CYP450IID6 CYP450IIIA4 enzymes
      Also FDA-approved for treatment of adult and pediatric obsessive compulsive disorder (OCD), bulimia, pediatric depression
Paroxetine (Paxil) Clinically insignificant decreases in heart rate Unknown Inhibitor of CYP450 IID6 enzyme
      Also FDA-approved for treatment of social phobia, panic disorder, OCD, generalized anxiety disorder (GAD)
Sertraline (Zoloft) None known   In high doses, inhibitor of CYP450 IID6 enzyme
      Also FDA-approved for treatment of panic disorder, adult and pediatric OCD, post-traumatic stress disorder (PTSD)
Fluvoxamine (Luvox) None known   Potent inhibitor of multiple CYP450 enzymes
      Also FDA-approved for treatment of adult and pediatric OCD
Citalopram (Celexa) None known    
Escitalopram (Lexapro) None known   SSRI with most selective binding to serotonin transporter
Venlafaxine (Effexor) Arrhythmia or cardiac block in overdose Unknown No significant inhibition of CYP450 enzymes
  Increased diastolic blood pressure in doses > 300 mg/d Presynaptic inhibition of norepinephrine reuptake Side-effect profile similar to SSRIs
Presynaptic alpha2-receptor antagonist      
Mirtazapine (Remeron) None known Postsynaptic histamine1-receptor blockade Very sedating in low doses
      Weight gain
      Minimal sexual side effects
      No significant inhibition of CYP450 enzymes
Dopamine and norepinephrine reuptake inhibitor      
Bupropion (Wellbutrin; Zyban) Significant increases in blood pressure in patients with preexisting hypertension Presynaptic inhibition of norepinephrine reuptake No significant inhibition of CYP450 enzymes
      Minimal sexual side effects
      Not proven effective in the treatment of anxiety disorders
      FDA-approved for treatment of nicotine dependence
Atypical serotonergic agents      
Trazodone (Desyrel) Orthostatic hypotension Postsynaptic alpha1-receptor blockade Sedation, confusion, dizziness
  Cardiac arrhythmias rare unknown Rare cases of priapism
Nefazodone (Serzone) Sinus bradycardia unknown Similar side-effect profile as trazodone (except without priapism)
      Minimal sexual side effects
      Potent inhibitor of multiple CYP450 enzymes
      Liver failure rare
Dextroamphetamine (Dexedrine) Rarely increases blood pressure or induces tachycardia in therapeutic doses Release of dopamine and catecholamines Avoid in patients with hyperthyroidism, severe hypertension, severe angina, tachyarrthythmias
Methylphenidate (Ritalin)      
Benzodiazepines   Allosteric alteration of GABAA receptors Rapid relief of anxiety symptoms
Alprazolam (Xanax)      
Clonazepam (Klonopin)      
Lorazepam (Ativan) Hypotension Muscle relaxation of GABAA spinal cord receptors Can cause fatigue, ataxia, drowsiness, amnesia, and behavioral dyscontrol
Oxazepam (Serax)     Relatively safe in overdose
Partial 5-HT1A-receptor agonist      
Buspirone (BuSpar) None known   FDA-approved for treatment of GAD
Omega1-receptor agonist      
Zolpidem (Ambien) None known Potentiation of GABAA receptor Sedating
Zaleplon (Sonata) None known    
Lithium Sinus node dysfunction
Sinoatrial block
T-wave inversion or flattening, particularly in patients >60 years of age
Arrhythmias and sudden death in patients with cardiac disease
Unknown Narrow therapeutic index (.6-1.2 mmol/L)
Many medications alter lithium plasma levels*
Fatal in overdose
Mood stabilizer for patients with bipolar disorder
Yearly ECG in patients over 50

* Medications that increase lithium levels: nonsteroidal anti-inflammatory drugs, diuretics (thiazides, ethacrynic acid, spironolactone, triamterene), angiotensinconverting enzyme inhibitors, metronidazole, tetracycline. Medications that decrease lithium levels: acetazolamide, theophylline, aminophylline, caffeine, osmotic diuretics.

ABBREVIATION: GABA = gamma-aminobutyric acid.