Cessation of clozapine-induced severe hypersalivation along with improvement of residual persistent auditory hallucinations by tDCS in a patient of chronic schizophrenia - A case report.

Sir,

A 47-year-old male, case of treatment-resistant schizophrenia, had presented with refractory auditory hallucinations, delusion of persecution, and reference at our center.

The patient had a continuous progressive illness of 20 years with good compliance to treatment. Initially, he had positive symptoms such as thought broadcast, delusion of persecution, and derogatory auditory hallucinations. In the course of treatment, the symptoms responded with medications and ECT. However, the auditory hallucinations remained refractory to treatment.

In 2010, the patient was started on clozapine, which was gradually escalated up to 450 mg. In 2016, haloperidol was added for augmentation, still the hallucinations persisted. Hypersalivation was noted ever since the patient was started on clozapine. Glycopyrrolate (4 mg) was added for the same; however, minimal improvement was noted. In 2020, when the patient was taken for tDCS therapy in view of refractory auditory hallucinations, he was already on clozapine (450 mg) and glycopyrrolate (4 mg).

The patient received tDCS sessions on an outpatient basis after taking informed consent. The target areas of stimulation were left temporoparietal junction as the cathode and right dorsolateral prefrontal cortex as the anode. The intensity was kept at 2 mA and stimulation was given for 30 minutes once daily on weekdays.

At the end of 15 sessions, there was a significant decline in PANSS scores (composite score reduced from 11 to 3) along with a near-complete cessation of auditory hallucinations.

It was observed that not only hallucinations but hypersalivation also improved significantly. Even in the follow-up visits, hypersalivation did not remain a major concern as previously. However, the patient continued to take 4 mg of glycopyrrolate.

DISCUSSION

The causes of hypersalivation, a distressing side effect that occurs in 31%–54% of patients receiving clozapine therapy, are nonspecific.[1]

It may be mediated by the imbalance between M3 receptor blockade (decrease in salivation) and M4 receptor stimulation (increase in salivary output). Another explanation is that clozapine interferes with the swallowing reflex, leading to the pooling of saliva and, therefore, patient complaints of hypersalivation.[2]

tDCS administered to the hyperactive left temporoparietal junction (“inhibitory” cathodal) and to the hypoactive left dorsolateral prefrontal cortex (“excitatory” anodal) improves refractory hallucinations as studied earlier.[3] However, the action of tDCS on clozapine-induced hypersalivation has not been noted earlier.

It has also been reported that anodal tDCS projecting to the swallowing sensorimotor cortical acts on cricopharyngeal muscles and improves swallowing.[4] Bihemispheric anodal tDCS has been applied to better modulate the excitability of esophageal cortex (proximal to pharyngeal cortex) and improve dysphagia.[5]

Nitsche et al.[6] have also stated that tDCS mediates increase in catecholamine through neuroplastic changes.

The above-mentioned theories could possibly explain the improvement in hypersalivation in this case.

CONCLUSION

Although no direct association of tDCS on clozapine-induced hypersalivation has been observed or reported earlier, the above case suggests a temporal correlation between the two. Effect of tDCS through its action on pharyngeal musculature or by catecholaminergic changes could be a topic of further research. tDCS could also be used as an adjunct to pharmacotherapy in treating clozapine-induced hypersalivation.

Declaration of patient consent

The authors certify that they have obtained all appropriate patient consent forms. In the form, the patient has given his consent for his images and other clinical information to be reported in the journal. The patient understands that his 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.