• In addition to individual preference, the choice of antidepressant medication should depend on evidence of efficacy, the likely impact of potential adverse effects, and the person's current medication:
• Selective serotonin reuptake inhibitors (SSRIs) are most commonly used.
• SSRIs can worsen motor symptoms, but this occurs rarely.
• SSRIs should not be used by people taking selegiline or rasagiline (risk of serotonin syndrome).
• Use SSRIs with caution in people taking entacapone or tolcapone (theoretical risk of serotonin syndrome).
• Tricyclic antidepressants may be more effective than SSRIs in people with Parkinson's disease, but their use is limited by the risk of adverse effects. They should only be used with caution.
• Avoid tricyclic antidepressants in people with postural (orthostatic) hypotension, falls, or dementia.
• Tricyclic antidepressants should not be used without specialist advice by people taking selegiline or rasagiline (risk of serotonin syndrome).
• Use tricyclic antidepressants with particular caution in people taking entacapone or tolcapone (theoretical risk of serotonin syndrome).
• People taking selegiline or rasagiline may cautiously use trazodone or mirtazapine (off-label use for selegiline).
• There are no known contraindications to the use of any type of antidepressant in people taking amantadine, apomorphine, or oral and transdermal dopamine agonists.
• Other antidepressants:
• Irreversible monamine oxidase-A inhibitors (phenelzine, isocarboxazid, tranylcypromine) should not be used with levodopa, selegiline, rasagiline, entacapone, or tolcapone (risk of hypertension).
• Moclobemide should not be used with selegiline or rasagiline, and should be used with caution in people taking entacapone, tolcapone, and levodopa (risk of hypertension).
• Venlafaxine and duloxetine should not be used by people taking selegiline or rasagiline, and used with caution in those taking entacapone, or tolcapone (risk of serotonin syndrome).
• Consider contacting the person's Parkinson's disease specialist to ensure that their anti-parkinsonian medication regimen is optimal.
• Seek specialist advice if:
• There is doubt about whether an antidepressant can be safely prescribed.
• There is suspicion that the antidepressant prescribed may be affecting motor control or causing adverse effects.

• The National Institute for Health and Clinical Excellence guideline, Depression: the treatment and management of depression in adults with chronic physical health problems includes a table of drug interactions and recommended antidepressants for people with Parkinson's disease who are taking anti-parkinsonian medication. For further details, see Appendix 16 (pdf).

These recommendations are in line with a guideline published by the National Institute for Health and Clinical Excellence (NICE), Parkinson's disease: national clinical guideline for diagnosis and management in primary and secondary care [NICE, 2006], and the NICE guideline Depression in adults with a chronic physical health problem [NICE, 2009].

• On the basis of a Cochrane systematic review (last assessed as up-to-date in February 2003) of three small randomized controlled trials (RCTs) [Ghazi-Noori et al, 2003] and two subsequent small RCTs, NICE concluded that there was insufficient evidence of the efficacy or safety of any form of treatment for depression in Parkinson's disease [National Collaborating Centre for Chronic Conditions, 2006].
• Other systematic or evidence-based reviews have differing conclusions: that antidepressant drugs are ineffective for depression in Parkinson's disease [Weintraub et al, 2005]; that they are effective for depression in Parkinson's disease [Raskind, 2008]; or, that tricyclic antidepressants may be more effective than SSRIs [Miyasaki et al, 2006; Frisina et al, 2008a]. However, most primary studies are small and of poor quality.
• Three small RCTs have been published since the NICE guideline [Antonini et al, 2006; Devos et al, 2008; Menza et al, 2008]. In particular, one small but well-conducted trial found the tricyclic antidepressant nortriptyline to be significantly more efficacious than paroxetine, and equally well tolerated [Menza et al, 2008].
• A survey of US neurologists carried out in the 1990s (when SSRIs were a relatively new class of antidepressant) found that, even then, more than half used SSRIs as first-line treatment for depression in people with Parkinson's disease [Richard and Kurlan, 1997].
• Although there are case reports of SSRIs worsening motor symptoms [Jimenez-Jimenez et al, 1994; Lemke, 2008], this is thought to be rare.
• An evidence-based review reported that data from around 500 participants in open-label or retrospective studies suggest that worsening of motor symptoms by SSRIs is rare [Lemke, 2008].
• A systematic review reported that, in open-label trials, 86% (202/234) of people taking an SSRI completed active treatment [Weintraub et al, 2005].
• The recommendation to avoid tricyclic antidepressants in people with postural (orthostatic) hypotension and falls is pragmatic and based on expert opinion [Miyasaki et al, 2006].
• Other recommendations with regard to potential drug interactions are derived from: publications from the Parkinson's Disease Society aimed at primary care professionals [Parkinson's Disease Society, 2003; Parkinson's Disease Society, 2007]; a narrative review, Depressive symptoms in Parkinson's disease [Lemke, 2008]; and the textbook, Stockley's drug interactions [Baxter, 2008].
• SSRIs or tricyclic antidepressants should not be used with selegiline or rasagiline because of the risk of serotonin syndrome. Entacapone and tolcapone should be used with caution with SSRIs and tricyclic antidepressants because serotonin syndrome is a theoretical risk. However, there are no documented reports of this occurring.
• There are no case reports of serotonin syndrome or an increase in adverse effects occurring when trazodone or mirtazapine are used with drugs for Parkinson's disease, or when dopamine agonists, apomorphine, or amantadine are used with any type of antidepressant.
• However, the manufacturer's Summary of Product Characteristics for selegiline states that it should not be given with any type of antidepressant [ABPI Medicines Compendium, 2010].
• Irreversible monoamine oxidase inhibitors should not be used with levodopa, selegiline, rasagiline, entacapone, or tolcapone because of an increased risk of hypertension. Moclobemide should not be used with selegiline or rasagiline for the same reason.
• Venlafaxine and duloxetine should be used with caution in people taking selegiline, rasagiline, entacapone, or tolcapone because of an increased risk of serotonin syndrome.
• The recommendation to consider contacting the person's Parkinson's disease specialist to ensure that their anti-parkinsonian medication regimen is optimal is based on very limited evidence from narrative reviews that some anti-parkinsonian medications (selegiline and pramipexole) may have antidepressant properties [Horstink et al, 2006; Lemke, 2008; Raskind, 2008].