Sports Pharmacology of Psychiatry and Behavioral Medicine

Introduction

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Often, an optimal treatment regimen is determined through a collaborative approach, including team physicians, psychologists, psychiatrists, athletic trainers, academic advisors, coaches, teammates, parents, and administrative staff. The following nonprescription therapies have been shown to be helpful:
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  Psychotherapy
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  Over-the-counter herbal and dietary supplements
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  Light therapy (for seasonal affective disorder)
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  Electroconvulsive therapy (ECT) (treatment-resistant manic or mixed episodes; bipolar disorder; highly symptomatic, dysfunctional, or suicidal major depressive disorder)
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Athletes often self-treat their conditions with the following:
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  Overtraining
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  Avoidance
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  Self-help information
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  Self-medication with over-the-counter medications, alcohol, and illicit drugs
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Treatment with medications requires evaluation and monitoring:
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  Accurate diagnosis and identifying existing comorbidities
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  Suicidal ideation, self-harm
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  Side effects, effects on school/work/sport performance
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  Efficacy and compliance
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  Attention to potential side effects that may affect athletic performance:
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    Daytime sedation
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    Orthostasis
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    Tremors
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    Arrhythmias
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    Nausea
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    Weight gain or loss

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Table 9.1 lists syndromes associated with the medications reviewed in this chapter: neuroleptic malignant syndrome (NMS), serotonin syndrome (SS), and extrapyramidal symptoms (EPS).

TABLE 9.1

SYNDROMES ASSOCIATED WITH MEDICATIONS USED FOR PSYCHIATRIC DISORDERS

Serotonin Syndrome (Italics distinguish from NMS)	• Potentially fatal, caused by net increase in serotonin • Occurs rapidly after medication change (usually within 24 hours) • Symptoms include anxiety, agitation, disorientation, and delirium; autonomic (dilated pupils, tachycardia, hypertension, hyperthermia, diaphoresis, vomiting, and diarrhea); and neuromuscular (hyperrigidity , myoclonus , hyperreflexia , tremor , akathisia, ataxia, and shivering) • Treatment: discontinue serotonergic drugs; supportive management with intravenous fluids, oxygen, blood pressure control, benzodiazepine to control agitation, and cyproheptadine (if other treatments fail)
Neuroleptic Malignant Syndrome (Italics distinguish from serotonin syndrome)	• May be a life-threatening emergency • Often develops over days • Symptoms include mental status changes (confusion, agitated delirium, mutism, and catatonic); muscular rigidity (lead-pipe rigidity/cogwheeling), bradyreflexia , hyperthermia, tremor, diaphoresis, tachycardia, and labile blood pressure • Treatment: hospitalization; discontinue offending agent; consider benzodiazepines, dantrolene, bromocriptine, or amantadine and supportive care
Extrapyramidal Symptoms (EPS)	• Range of movement disorders: dystonia (muscular spasms of neck, jaw, and back), akathisia (restlessness, nervousness, and anxiety), parkinsonism (rigidity, tremor, bradykinesia, shuffling gait, and masked facies), and tardive dyskinesia (involuntary muscle movements of distal extremities and face) • Treatment: consider anticholinergic drugs, beta-blockers, benzodiazepines, and pramipexole

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Use caution with medication selection in pediatric, pregnant, potentially pregnant, or geriatric patients.

Treatment for Major Depressive Disorder (MDD)

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Table 9.2 summarizes antidepressant classification and adverse effects.

TABLE 9.2

MEDICATIONS USED FOR DEPRESSION AND/OR ANXIETY

Name (Brand)	Mechanism, Adverse Effects (AEs), Comments
Selective Serotonin Reuptake Inhibitor (SSRI)	• AEs: Sexual dysfunction, drowsiness, weight gain, insomnia, anxiety, dizziness, headache, dry mouth, blurred vision, rash-itching, tremor, constipation, and stomach upset • Caution with the use of nonsteroidal anti-inflammatories, gastrointestinal bleeding and serotonin syndrome
Citalopram (Celexa)	• Some antihistamine effect
Escitalopram (Lexapro)	• Best tolerated, fewest drug interactions
Fluoxetine (Prozac)	• Activating properties (not good with insomnia and anxiety) • Lowest rate of withdrawal symptoms • Long half life
Paroxetine (Paxil)	• Calming, good for anxiety
Paroxetine CR (Paxil CR)	• Highest rate of withdrawal due to AEs • Highest rate of sexual AEs (16%)
Sertraline (Zoloft)	• Activating properties • Diarrhea (common)
Serotonin Noradrenergic Reuptake Inhibitor (SNRI)	• Not interchangeable, have different levels of NE and 5HT action • Common AEs: nausea, somnolence, dry mouth; dizziness, constipation, weakness; blurred vision, sweating
Desvenlafaxine (Pristiq)	• Hypertension may occur during titration • Withdrawal reaction • Headache, anxiety, insomnia, and diarrhea
Duloxetine (Cymbalta)	• Good for depression with chronic pain • Less risk of hypertension than venlafaxine • 67% higher discontinuation due to AEs • Start twice daily then switch to once daily dosing
Levomilnacipran (Fetzima)	• Enantiomer of milnacipran • Has the most noradrenergic action of SNRIs
Venlafaxine (Effexor)	• First-line SNRI, most often prescribed • Hypertension may occur during titration • Has 52% higher (nausea, vomiting) AE incidence than SSRIs as a class • 40% higher risk of discontinuation due to AEs • Highest rate of withdrawal symptoms • XR form lower in AE
Serotonin Antagonist and Reuptake Inhibitor (SARI)	• Mechanism: antagonize serotonin receptor and inhibit reuptake of serotonin, norepinephrine, or dopamine
Trazodone (Desyrel)	• Priapism • Lower dose increases somnolence (may improve sleep)
Vilazodone (Viibryd)	• Titrate dose per recommendations • Diarrhea, nausea; sexual dysfunction; dizziness, insomnia, vomiting; dry mouth
Other Mechanisms
Mirtazapine (Remeron, Remeron SolTab)	• Mechanism: noradrenergic and specific serotonergic antidepressant (NaSSA) has some alpha-adrenergic and serotonergic properties • Weight gain, sedation • Associated with weight gain (1.8–6.6 lb) after 6–8 weeks • Faster onset of action • Sedation decreases with increased dose
Bupropion (Wellbutrin)	• Mechanism: norepinephrine and dopamine reuptake inhibitor (NDRI), is both an active drug and precursor • Weight loss • Activating and energizing properties • Low incidence of sexual dysfunction • XR form available
Buspirone (Buspar)	• Mechanism: selective serotonin 5HT1A receptor agonist and dopamine agonist/antagonist • Off label to augment major depressive disorder • May have role in anxiety if unable to tolerate SSRIs or SNRIs. May not work as well if patient was on long-term benzodiazepine • Multiple dosing may be a drawback
Tricyclic Antidepressants (e.g., amitriptyline, nortriptyline, and clomipramine)	• Dangerous and lethal in overdose (QT prolongation leading to arrhythmias) • Mechanism increases neurotransmitter by inhibiting reuptake of primarily serotonin and norepinephrine • Not used much due to dose-related AEs; potential cardiotoxicity; anticholinergic, antihistamine, and sedating effects; sexual dysfunction; diaphoresis; tremors; and acute hepatitis • Decrease seizure threshold • Evaluate for cardiac risk factors, consider ECG in patients aged >40 years • Onset of action may take 4 weeks • Taper to avoid withdrawal
Monoamine Oxidase Inhibitors	• Mild anticholinergic (AEs: sedation, agitation, orthostatic hypotension, dizziness, GI effects, weight gain, and suppressed REM sleep) • Not often used due to diet restrictions, drug interactions, and AEs • Risk of SS
Benzodiazepines (e.g., alprazolam, lorazepam, clonazepam, and diazepam)	• AEs: Sedation, nausea, syndrome of inappropriate antidiuretic hormone secretion, blood dyscrasia, hyponatremia, anterograde amnesia, agitation, depression, cognitive impairment, hyponatremia, and extrapyramidal syndrome • Used in combination in acute settings of mania/hypomania, particularly to reduce agitation in patients with acute mania • Risk of tolerance and addiction • Monitor complete blood count and liver function for long-term use • Contraindicated in patients with myasthenia gravis or acute narrow-angle glaucoma • Caution in patients with substance abuse