Side Effects of Haloperidol (Haldol®) to Treat Chronic Regurgitation in California Sea Lions
Regurgitation is sporadically observed with various cetaceans and pinnipeds, most notably killer whales (Orcinus orca), false killer whales (Pseudorca crassidens), Pacific walrus (Odobenus rosmarus), and California sea lions (Zalophus californianus). In most instances, individuals consume the regurgitant and no problems arise. On occasion, individuals loose weight due to competition with conspecifics over the regurgitated material or loss of calories from regurgitated material dissipating into the water. In this paper we present successful treatment of regurgitation in two California sea lions using the antipsychotic drug Haloperidol and report side effects which may limit its use in a community setting.
Haloperidol is an antipsychotic drug in the family of Phenylbutylpiperidines, structurally related to the Phenothiazines. In low doses it has been a very effective antiemetic in humans. As a group, these agents are dopamine receptor antagonist with varying degrees of selectivity among the cortical dopamine tracts. Specific sites of effect include the nigrostriatal tract responsible for extrapyramidal side-effects (EPS) such as tardive dyskinesia (TD, rhythmic involuntary movements of face and extremities), neuroleptic malignant syndrome (NMS, hyperthermia, and autonomic disturbances such as cardiac arrhythmias and dyspnea), pseudoparkinsonism signs (tremors, rigidity, and shuffling gait), and dystonias (neck muscle spasms, extensor rigidity of back muscles, hyperreflexia, torticollis, retrocollis, opisthotonos, dysphagia). Other, less specific side effects include sedation orthostatic hypotension. With the exception of NMS, these side effects are reversible within 24 to 48 hours after drug withdrawal.1
Two California sea lions, one ten-year-old in a training program, and the other a three-year-old in an exhibit pool, presented for weight loss due to chronic regurgitation. Medical examinations including CBC, serum chemistries, heavy metal analysis, radiography, and endoscopy proved normal and training techniques such as placing the behavior on a stimulus control and then attempting to extinguish the behavior or ignoring the behavior failed to change the condition. Placing the animals in competitive social grouping of conspecifics and medical intervention using Prozac (Fluoxetine®) at various doses and metoclopramide (Reglan®) and Cisapride® also failed to affect the behavior.
Within five days of instituting Haloperidol at 0.06 mg/kg orally twice daily given with one fish followed by multiple training and exercise sessions lasting about 30 minutes, regurgitation significantly diminished in one animal and resolved in the other. Soon after initiating therapy, both sea lions developed a stilted, stiff legged gate, moderate sedation and a shortened attention span. Certain trained behaviors such as clapping and fine motor facial behaviors, such as smiling and tongue movements, appeared difficult and even required relearning. Both sea lions stopped regurgitating and within two months were back to target weights. Side effects diminished, and the animals' behaviors returned to near normal.
Approximately three months after dispensing Haloperidol to the exhibit California sea lion, a pool mate presented with odd behaviors consisting of opisthotonus and fasciculations of the epaxial muscles. These clinical signs resolved within four hours without symptomatic therapy. Several days later another pool mate presented hunched with similar muscular fasciculations, followed by three others over the next six months. Differentials including vitamin E/selenium deficiency, domoic acid toxicity, and Zn toxicity were ruled out.
This community pool holds 13 California sea lions of varying ages and sexes. After reviewing the feeding practices of this area we discovered the animals presenting with these odd neurologic clinical signs were the most aggressive eaters and, on occasion, were observed to induce the individual under treatment to regurgitate the fish containing medication. To answer the question of whether Haloperidol could induce these clinical signs three individuals, two which had presented multiple times and one which had never presented, were separated from their pool mates and fed a fish containing one half the calculated dose of Haloperidol. Two of the three animals exhibited hunching with moderate epaxial muscle fasciculations, one from the former group and the individual with no clinical history.
Based on this experience, keepers were asked to split the medication into one-quarter doses to limit the amount of medication that an aggressive pool mate could receive. For several months this proved successful, however two individuals subsequently presented with hunching and muscle fasciculations. Modifications to feeding practices such as separating individuals proved impossible in the community setting so the decision was made to withdraw Haloperidol. Knowing that abrupt withdrawal of the drug may produce recurrence of regurgitation, weaning is expected to take from six months to a year.
A similar case by Dalton et al.2 required a Haloperidol dose of 0.11 mg/kg, two times greater than our dose, with not apparent side effects. Although our experiment included a nonsignificant sample size we are confident the side effects of dystonia and pseudoparkinsonism were a result of Haloperidol administration. The explanation for lack of side effects in the treated individuals, other than the mild pseudoparkinsonism, and the extreme dystonia in individuals receiving lower than therapeutic doses is unclear at this time. Based on this experience we recommend the use of Haloperidol for the treatment of weight loss due to regurgitation in California sea lions but do not recommend treatment of individuals in a community setting unless one is able to tightly control the administration of the drug.
1. Antipsychotic Agents. 2003. In: Killion K.H. and E.K. Kastrup (eds.). Drug Facts and Comparisons, Wolter Kluwer Health, Inc., St. Louis, Missouri. Pp. 933-947.
2. Dalton LM, Robeck TR, Young G. 1997. Aberrant behavior in a California sea lion (Zalophus californianus). Proceedings of the 27th Annual Internation Association for Aquatic Animal Medicine. Pp. 137.