Depression, common in geriatric patients, traditionally has been treated with tricyclic antidepressants (TCAs). However, a
growing body of literature indicates that selective serotonin reuptake inhibitors (SSRIs) are as effective as TCAs in the
treatment of depression, and have fewer side effects.1,2,3,4
Paroxetine is a phenylpiperidine derivative and is the most potent inhibitor of the reuptake of serotonin (5-hydroxy-tryptamine,
5-HT) of all available antidepressants, including the SSRI class.5 Paroxetine is approved for the treatment of depression, obsessive-compulsive disorder, panic disorder, and social phobia.
It is also used in the treatment of generalized anxiety disorder, posttraumatic stress disorder, premenstrual dysphoric disorder,
and chronic headache.5,6
Contraindications for paroxetine include concomitant use in patients taking monoamine oxidase inhibitors (MAOIs) or thioridazines.6 Caution should also be taken when prescribing paroxetine concomitantly with warfarin, sumatriptan, drugs affecting hepatic
metabolism, drugs metabolized by cytochrome P45011D6, TCAs, lithium, digoxin, and diazepam. Adverse effects involve multiple
organ systems, including cardiovascular, respiratory, gastrointestinal, urogenital, dermatologic, musculoskeletal, and neurologic.
Neurologic side effects include somnolence, dizziness, insomnia, nausea, anxiety, paresthesias, decreased libido, dragged
feeling, confusion, and tremor.5,6 Movement disorders, including dyskinesias, have also been reported.6
While paroxetine can significantly improve mood, side effects such as tremor can be disabling. Despite an abundance of literature
identifying tremor as a side effect of paroxetine, the literature fails to discuss the functional consequences of this adverse
effect. We describe two cases of paroxetine-induced tremor and its effect on patient function in a geriatric subacute rehabilitation
setting.
Case studies The following cases represent patients admitted to a restorative subacute rehabilitation unit in an institution specializing
in the care of geriatric patients. Progress in physical therapy (PT) and occupational therapy (OT) was measured with the functional
independence measure (FIM(tm)). This tool is an ordinal scale that measures the severity of a patient's disability, including
self-care, sphincter control, mobility-locomotion, communication, and social cognition. The following scales are used: 1)
total assistance, 2) maximal assistance, 3) moderate assistance, 4) minimal assistance, 5) supervision, 6) modified independence,
and 7) independence.7
Case 1 An 85-year-old female was admitted to an acute hospital for a right shoulder dislocation secondary to a fall. She was treated
with a closed reduction. After six days, the patient was transferred to subacute rehabilitation. She was not allowed weight-bearing
activity or range-of-motion to the right upper extremity.
The patient's past medical history included hypertension, syncope, dementia, and urinary incontinence with urinary tract infection
(UTI). Her medications upon the transfer were aspirin, 81 mg/d, losartan, 50 mg/d, hydrochlorothiazide, 25 mg/d, and levofloxacin,
250 mg/d. Prior to the fall, the patient was independent in ambulation. Due to her symptoms of depression, paroxetine, 10
mg at night, was added to her treatment regimen after the transfer. PT and OT were initiated the next day. Initial functional
evaluations revealed that the patient needed moderate assistance for bed mobility, moderate- to- maximal assistance for transfers,
and was unable to ambulate.
Two weeks after the start of therapy, the patient's functional status improved. She needed only minimal- to- moderate assistance
for bed mobility, minimal- to- moderate assistance for transfers, and she was able to walk 50 feet with a platform rolling
walker and moderate assistance.
Three weeks after the transfer to the subacute rehabilitation institute, the orthopedic surgeon allowed her full weight bearing
of the right upper extremity, with no range-of-motion restrictions. At this point, physical and occupational therapists reported
the onset of a severe upper body intentional tremor (begins and increases in intensity as a limb moves toward an object, such
as when the patient reaches to grasp an object). The therapists noted that the decline started suddenly at 3 weeks after transfer and start of paroxetine. The resulting functional
decline included the inability to ambulate, despite assistive devices and assistance from the therapists. Paroxetine was discontinued
secondary to the tremor.
One week after the discontinuation of paroxetine, the patient's functional status improved. However, the patient did not reach
her previous baseline as evidenced by her lower FIM one week after cessation of paroxetine. She required close supervision
for bed mobility, moderate assistance for transfers, and was able to ambulate 15 to 50 feet with a rolling walker and personal
assistance. Upon discharge from the subacute unit 6 weeks after admission, she was able to ambulate 100 feet with a rolling
walker and contact guard, and negotiate 4 steps with minimal assistance. However, the patient's function was still less than
normal after the tremor ceased.
Case 2 A 79-year-old female was admitted to an acute hospital for a UTI and weakness on the right side of her body. Computed tomography
of her brain was unremarkable. She was treated with trimethoprim/sulfamethoxazole, one double-strength tablet every 12 hours
for 5 days. After 4 days, she was transferred to subacute rehabilitation.
The patient's past medical history was significant for hypertension, Alzheimer's dementia, osteoporosis, kyphosis, and pneumonia.
Her medications upon transfer included digoxin, 0.125 mg/d, aspirin, 325 mg/d, zolpidem, 10 mg at bedtime, subcutaneous heparin,
5,000 units/bid, trimethoprim/sulfamethoxazole, one double-strength tablet every 12 hours, and paroxetine, 10 mg at bedtime.
Her UTI resolved after treatment with antibiotics, and her right-sided weakness had improved upon admission to subacute rehabilitation.
Initial evaluation was significant for mild right lower extremity weakness and severe bilateral upper extremity tremor. According
to the patient's daughter, the tremor was of recent onset. Functional evaluation upon admission to subacute rehabilitation
revealed that the patient needed minimal- to- moderate assistance for bed mobility, moderate assistance from two persons for
transfers, and was unable to stand or ambulate. PT/OT was initiated the next day. At this time, paroxetine was discontinued
because of the tremor. Within 5 days, the tremor subsided, and the patient's functional status improved. She required minimal
assistance for bed mobility and transfers, and was able to ambulate 10 feet with hand-held assistance. Twelve days after admission
to subacute rehabilitation, she was able to ambulate 50 feet with hand-held assistance. Upon discharge, she was able to ambulate
for 150 feet with hand-held assistance.
Discussion Paroxetine has been successfully used in treating depression. Multiple studies have proven it is effective and well tolerated.1-4
Tesei's study1 assessed the tolerability of paroxetine at a dose of 10 to 20 mg/d in 65 outpatients (age 65.1 8.5) with Parkinson's disease
(PD) and depression. Using the Hamilton Depression Rating Scale (HDRS) to measure depression, treatment was continued for
125.3 89.6 days in 52 patients. The HDRS improved from 21.76.4 to 13.85.8 (p<0.001). Thirteen patients stopped paroxetine because of an adverse reaction, yet only 2 patients reported tremor that reversed
after the treatment was stopped. Researchers concluded that paroxetine is a safe and effective drug to treat patients with
depression in PD.1
Erfurth et al concluded that paroxetine (10 to 40 mg/d) was well tolerated and led to a greater than 50% reduction in HDRS
score in 8 out of 9 patients with neurologic disease (age range: 22 to 71).2 Aberg-Wistedt's group studied the effects of paroxetine (20 to 40 mg/d) in 177 patients (mean age 42, 71% female) with unipolar
depression. They concluded that paroxetine was well tolerated and there was significant improvement in quality of life and
reductions in Axis II personality psychopathology.3
Paroxetine has also been reported to have no significant effect on gait in healthy older people. In a randomized, crossover,
four-period, double-blind, placebo-controlled laboratory trial by Draganich et al, 12 healthy older subjects (average age
67, age range 65 to 72) were tested. Subjects were randomized to 1 of 3 antidepressant drugs (amitriptyline, 50 mg; desipramine,
50 mg; and paroxetine, 20 mg), or a placebo; drugs were given four hours prior to gait testing. Gait testing took approximately
45 minutes to perform. Temporal-distance measures and kinematics of the lower limb, including gait velocity, cadence, and
angular velocity of hip flexors and knee flexors were measured. The results revealed no significant effect for obstructed
and unobstructed gait in subjects taking paroxetine.4
SSRI: adverse events Movement disorders are a noted side effect of all SSRIs, including paroxetine.8
Lane's review reported that SSRIs induce extrapyramidal symptoms (EPS), akathisia, or both, possibly due to serotonergically-mediated
inhibition of the dopaminergic system.9 Caley also noted that the EPS occurring with SSRI use involves serotonin's inhibitory actions on extrapyramidal dopamine
activity.10
A review by Gerber and Lynd found a total of 127 published reports of SSRI-induced movement disorders including akathisia
(n=30), dystonia (n=19), dyskinesia (n=12), tardive dyskinesia (n=6), parkinsonism (n=25), mixed disorders (n=15), bruxism
(n=10), and unclassified movement disorders (n=10).11 Leo reviewed 71 cases of SSRI-induced EPS, and found the most common were akathisia (45.1%), dystonia (28.2%), parkinsonism
(14.1%), and tardive dyskinesia-like states (11.3%). Fluoxetine was implicated in 74.6% of the cases, and paroxetine was implicated
in 5.6% of the cases.12
Treating drug-related tremor Tremor is an important adverse effect of paroxetine. Not only is it disabling to the individual, but as evident in the cases
described, it can significantly impair functional recovery, especially during the rehabilitation process. The occurrence rate
of tremor depends on the dose of paroxetine used. At 20 mg/d, tremor occurs in 7.7% of patients; at 30 mg/d, the occurrence
is 7.9%; and at 40 mg/d, the occurrence is 14.7%.6
Paroxetine-related tremor is reversible. Treatment strategies include discontinuation of the medication; dosage reduction;
or the addition of a benzodiazepine, beta-blocker, or anticholinergic agent.11
Ceravolo observed fully reversible worsening of tremor in 1 of 29 depressed patients with PD who were enrolled in a study
to determine whether SSRIs worsen parkinsonian motor symptomatology.13 Lee and Nam reported the case of a 69-year-old female being treated for depression with paroxetine, 20 mg/d. Within 6 weeks
of treatment, she developed abnormal movements, most notably orobuccal and lingual dyskinesias; the symptoms were resolved
within 4 weeks of discontinuation of paroxetine.14 Edwards and Anderson recommend that paroxetine not be used as a first choice in patients prone to SSRI-related adverse reactions
and suggest the use of citalopram or sertraline instead, given their lower theoretical risk of drug interactions.15
Conclusion These cases demonstrate that the primary care physician should be aware of the potential of paroxetine to induce movement
disorders (especially tremor) and that this adverse effect can cause significant functional deterioration in a rehabilitation
setting. The key to timely treatment of paroxetine-related tremor is early diagnosis. Simple interventions, such as discontinuation
of paroxetine, can reverse this functional decline and lead to greater progress during the rehabilitation process.
Dr. Lai is resident physician, physical medicine and rehabilitation, Long Island Jewish Medical Center, New Hyde Park, NY.
Dr. Tolat is assistant professor, physical medicine and rehabilitation, Albert Einstein College of Medicine, and attending physician,
physical medicine and rehabilitation, Long Island Jewish Medical Center, New Hyde Park, NY.
Disclosure: The authors have no real or apparent conflict of interest with the subject under discussion.
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