Table 2.

Interventions to treat depression, including depressive symptoms in PD

Intervention
Drug class/ intervention strategy	Drug/intervention	Efficacy	Safety	Practice implications
Dopamine Agonists	Pramipexole	Efficacious	Acceptable risk without specialized monitoring	Clinically useful
	Pergolide	Insufficient evidence	Acceptable risk with specialized monitoring	Not useful
	Rotigotine	Unlikely efficacious	Acceptable risk without specialized monitoring	Investigational
Monoamine oxidase B (MAO‐B) inhibitors	Rasagiline	Insufficient evidence	Acceptable risk without specialized monitoring	Investigational
	Selegeline	Insufficient evidence	Acceptable risk without specialized monitoring	Investigational
	Moclobemide	Insufficient evidence	Acceptable risk with specialized monitoringa	Investigational
Tricyclic antidepressants	Nortriptyline	Likely efficacious	Acceptable risk without specialized monitoringb	Possibly useful
	Desipramine	Likely efficacious	Acceptable risk without specialized monitoringb	Possibly useful
	Amitriptyline	Insufficient evidence	Acceptable risk without specialized monitoringb	Possibly useful c
Selective serotonin reuptake inhibitors/selective serotonin norepinephrine reuptake inhibitors	Citalopram	Insufficient evidence	Acceptable risk without specialized monitoringe	Possibly useful d
	Sertraline	Insufficient evidence	Acceptable risk without specialized monitoringe	Possibly useful d
	Paroxetine	insufficient evidence	Acceptable risk without specialized monitoringe	Possibly useful d
	Fluoxetine	Insufficient evidence	Acceptable risk without specialized monitoringe	Possibly useful c
	Venlafaxine	Efficacious	Acceptable risk without specialized monitoring e	Clinically useful
Other antidepressants	Atomoxetine	Insufficient evidence	Acceptable risk without specialized monitoring	Investigational
	Nefazodone	Insufficient evidence	Unacceptable risk	Not useful
Alternative therapies	'Ω‐3 fatty acids	Insufficient evidence	Acceptable risk without specialized monitoring	Investigational
Nonpharmacological interventions	rTMS	Insufficient evidence	Acceptable risk without specialized monitoring f	Possibly useful (short term)
	CBT	Likely efficacious	Insufficient evidence g	Possibly useful

CBT, cognitive‐behavioral therapy; RCTs, randomized controlled trials; SSRI, selective serotonin reuptake inhibitors; TCA, tricyclic antidepressants.

^aCombined treatment with either TCAs or SSRIs carries an unacceptable risk.

^bTypical antimuscarinic adverse events have to be considered, such as dry mouth, constipation, urinary retention, and hyperhidrosis. Moreover, concomitant treatment of PD patients with TCAs can contribute to psychosis, sedation, and daytime sleepiness as well as to cognitive dysfunction or delirium when used in patients with PD dementia.2 The risk of mortality has to be considered if overdosing occurs. TCAs should be used with caution in patients with a history of urinary retention, angle‐closure glaucoma, increased intraocular pressure, cardiovascular disorders, and cognitive dysfunction. Of all the antidepressants, available data indicate that TCAs and citalopram at higher dosages pose the greatest risk for QT interval; Monoamine oxidase B prolongation in older adults.176

^cAlthough RCTs did not contain a placebo arm, the practice implication is ““possibly useful” because of proven antidepressant efficacy and license outside of PD.

^dAlthough RCTs for PD depression report conflicting data for efficacy, the practice implication is “possibly useful” because of proven antidepressant efficacy and license outside of PD.

^eThere are concerns about the induction of the serotonin syndrome when used in conjunction with the MAO‐B inhibitors selegiline and rasagiline.2 Hyponatremia may be associated with SSRI use, especially in elderly people with low body weight and concomitant use of diuretics, thought to be secondary to the development of the syndrome of inappropriate antidiuretic hormone.2 Of all the SSRIs available, data indicate that citalopram at higher dosages poses the greatest risk for QT prolongation in older adults (aged 60 years and above),176 such as regular electrocardiograph monitoring should be performed with citalopram when prescribed at a dose >20 mg/day in elderly patients.

^fThe FDA notes that labeling should include precautions for the use of rTMS devices in the treatment of patients with depressive or related conditions where safety and efficacy have not been established such as in movement disorders.177

^gIn general, the reporting of adverse events in CBT trials is limited;85, 86 in most behavioral health clinical trials, there is a lack of monitoring of adverse events, including serious adverse events such as suicide attempts, completed suicides, and psychiatric hospitalizations.86 Temporary increases in anxiety during behavioral health clinical trials are often considered a normal part of therapy and are therefore not documented as possible adverse events.86