INTRODUCTION
Fluvoxamine was originally developed as an antidepressant but it is also commonly used in the treatment of obsessive-compulsive disorder (OCD) with remarkable results in the recovery of these patients.[12] The treatment dosage is in the range of 100–300 mg/day titrated for 6–12 weeks. However, clinically significant improvement starts usually from 2nd week.[23] The most commonly reported side effects of fluvoxamine are nausea, headaches, sedation, diarrhea, decreased appetite, sleep disturbance, agitation, and urinary frequency, although these side effects tend to lessen during treatment or with a gradual dose reduction.[4] We present a case of the emergence of tics associated with fluvoxamine treatment.
CASE REPORT
A 21-year-old unmarried female presented in the psychiatry outpatient clinic of our institute with complaints of compulsions of checking things in her bag, repetitively checking the lock of her room if it is locked properly or not, trying to put her stationary items in a longitudinal symmetry on her study table, and repetitive gas knob checking for 1 year. She also developed an obsessive fear that her house will catch fire and it would be her fault because she has left gas stove knobs unlocked even when she knew her thoughts were irrational. She feels stressed when things are not orderly and often has obsessive doubts about misplacing things. Her symptoms were causing significant impairment in her socio-occupational functioning. She had no significant medical history and no history of involuntary muscle twitching or tics. Childhood history and family history were noncontributory. She was diagnosed with “obsessive and compulsive disorder with fair to good insight” (Code: F42) according to the Diagnostic and Statistical Manual of Mental Disorders, fifth edition (the American Psychiatric Association, 2013).[5] Tablet fluvoxamine 50 mg/day was started and after 3 weeks of therapy, her anxiety symptoms gradually improved. During the weeks of fluvoxamine treatment, there was an improvement in her symptoms although full recovery was not achieved. After approximately 4 weeks of fluvoxamine treatment, her dose was increased to 100 mg/day. She was reviewed after 4 weeks. She reported significant improvement in her compulsions but was still occasionally experiencing thoughts of doubt which she sometimes was able to overcome and sometimes led to compulsions. Her fluvoxamine dose was increased to 150 mg/day. After 1 week of increasing the dose, the patient began experiencing intermittent tension in her neck which was relieved by stretching of the neck, an itching before rotatory movement of the scapula, shrugging of the right side of the shoulder, and lateral stretching of her line of the lip. She reported that she had to repeat a particular movement until her tension was relieved. She could suppress her movements but required severe mental efforts. Physical examination and laboratory tests including complete blood count, renal and liver function tests, and thyroid function tests were all within normal range.
Even though a causal relation between fluvoxamine and tics was suspected, an electroencephalogram was done to rule out seizure activity; however, the reports were normal. On reducing the dose to 100 mg/day, these involuntary muscle movements decreased to full resolution after approximately 7 days with no deterioration/worsening of OC symptoms.
DISCUSSION
The patient's tics started during fluvoxamine treatment and completely stopped when the dose was reduced, suggesting a temporal relationship. To our knowledge, there are few reports involving the appearance or worsening of tics during fluvoxamine treatment,[678] as shown in Table 1.
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Table 1: Fluvoxamine and tics (review of literature)
The symptoms in this case report might be consistent with “Tic-related OCD with good or fair insight.” However, there was a significant improvement in the symptoms and subsequent onset of tics only after increasing the dose of fluvoxamine. Furthermore, the gradual resolution of tics in 7 days after reducing the dose with no deterioration of symptoms rules out the possibility of “Tic-related OCD with good or fair insight.”[59]
Previous studies document an overlap between Tourette syndrome (TS) and OCD suggesting that tics have their onset at a younger age than OCD. The obsessions in TS are more of aggressive, inappropriate sexual thoughts and images, and fear of saying inappropriate things, whereas compulsions are more of touching, blinking, and automatic imitative actions without awareness, nonobscene socially inappropriate acts, and self-injurious compulsions when compared to patients with OCD. The repetitive behaviors were viewed as achieving a satisfactory or “just right” state rather than avoiding a harmful event as in OCD and the absence of vocal tics excludes the possibility of TS.[10]
A complex mechanism of neurotransmission including reuptake or release of dopamine at its receptors as well as through the serotonergic action has been implicated in the causation of tics.[11] Antipsychotics used in the management of tic disorders reduce the tics by blocking these Type 2 dopamine receptors.[12] The appearance of tics during treatment with fluvoxamine might be due to an imbalance in the dopaminergic neurotransmitter system. A possible explanation can be that there are diffuse interconnections between serotonin (5-HT)-containing raphe nuclei and Dopamine-containing substantia nigra.[13] Electrical and neurophysiological studies suggest that the serotonin released by the raphe nuclei inhibits striatal neurons. Therefore, it is reasonable that selective serotonin reuptake inhibitors (SSRIs) by blocking the neuronal serotonin reuptake and increasing the availability of serotonin, may produce an effect similar to the dopamine blocking agents.[14] Tics are generated through abnormal activation of striatal neurons in the extracellular matrix proteins leading to unwanted inhibition of basal ganglia which acts as a brake on the movement pattern generators in the cerebral cortex and brainstem leading to disinhibition of movement generators leading to stereotypic tics. Consequently, it can be anticipated that movement disturbance might emerge from the use of SSRIs.[10]
Limitations
The patient was not rechallenged with fluvoxamine to reconfirm the diagnosis after the complete resolution of tics as the patient refused due to the fear of impairment in quality of life. Functional magnetic resonance imaging (MRI) can confirm the functional areas implicated in the pathophysiology of tics. However, due to financial constraints, functional MRI could not be done, which is also one of the limitations of our study. Furthermore, the genomic study was not done for better identification of genetic factors and to facilitate better understanding and vulnerability toward this impairing condition. Studies show that deficiency in the literature on SSRI-associated movement disorders, inadequate reporting of SSRI-induced movement disorders, and polypharmacy can become a significant hurdle in identifying these adverse effects associated with SSRIs.[15]
CONCLUSION
Our study may help clinicians develop a rationale for choosing appropriate SSRIs. It is important that the tics should be evaluated seriously as these are the sign of abnormal neuronal functioning. There is a need for extensive research on drug-induced tics before it can be understood how the drug pharmacodynamics affects the brain neuronal areas, the exact mechanism for the onset of tics, and the treatment options for the management of tics.
Psychoeducating patients regarding detailed workup and the importance of giving information to the clinician regarding concurrent medications hold considerable importance as it enhances their awareness to identify warning signs at the earliest. There is a need to closely observe the patients for the temporal relationship between drugs and the emergence of the side effects.
We believe that our case report may be a source of increasing awareness regarding tics as a potential side effect of fluvoxamine. This case report should be considered an exploratory study and future studies can further refine these results for explicit knowledge of the SSRI-induced tics or any other movement disorder.
Declaration of patient consent
The authors certify that they have obtained all appropriate patient consent forms. In the form, the patient has given her consent for her images and other clinical information to be reported in the journal. The patient understands that her name and initials will not be published and due efforts will be made to conceal identity, but anonymity cannot be guaranteed.
Financial support and sponsorship
Nil.
Conflicts of interest
There are no conflicts of interest.
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