Proceeding of the Institute for Zoo and Wildlife Research, Berlin, Germany (IZN) ISSN 1431-7338

1 Al Wabra Wildlife Preservation, PO Box 44069, Doha, State of Qatar; awwp.vet@alwabra.com
2 Leipzig Zoo, Pfaffendorfer Str. 29, 04105 Leipzig, Germany, keulenberger@zoo-leipzig.de

Extended Abstract

Summary
Designed as a human psychotropic, perphenazine is well known in zoo and wild animal medicine as a safe and effective tranquilizer. Its use in psittaciformes has not been reported. Perphenazine was used empirically in 6 individuals of 5 different parrot species: (Gang-Gang Cockatoo (Callocephalon fimbriatum), Scarlet Macaws (Ara macao), Palm Cockatoo (Probosciger aterrimus), Lilacine Amazon (Amazona autumnalis lilacina), Spix’s Macaw (Cyanopsitta spixii)) for therapies of feather damaging behaviour, aggression and appetite stimulus. The oily long acting formulas of perphenazine injections are ideal for long-term treatments and give an effective support in handling different psychological disorders in psittaciformes for up to six weeks. In the cases of the Palm Cockatoo and the Lilacine Amazon, it has been shown, that a thorough diagnostic evaluation is essential before using perphenazine. Careful consideration is needed before using, because it has not been approved yet for psittaciformes. It has been shown, that perphenazine can be a very effective support beside other therapies in handling different psychological disorders in psittaciformes.

Introduction
The use of perphenazine in wild ungulates and other wild animals is proven as a safe and effective tranquilizer (EBEDES, 1993; WINTERER and WIESNER, 1998). Designed as a human psychopharmaca (BALDESSARINI, 1985) it is now well known in zoo and wild animal medicine. The use in psittaciformes has not been reported yet. Perphenazine enanthate (2-(4-(3-(2-Chlorophenothiazin-10-yl)propyl)piperazin-1-yl)ethanol) is available as a 100 mg/ml solution (DECENTAN®).
Perphenazine, as part of the true long-acting tranquillizers, is a phenothiazine derivative with a piperazine side chain. It has properties similar to those described for the phenothiazine tranquillizers (UNGEMACH, 2002). It effects all levels of the central nervous system, particularly the hypothalamus, and demonstrates anxiolytic, anti-psychotic, and anti-emetic properties (SWAN, 1993).
The onset of effect of perphenazine enanthate in herbivores is slow, with sedation and calming effect in wild animals first noted about 12-16 hours after injection. Maximum or peak effect is usually observed on the third day, with duration of effect being up to seven days (EBEDES, 1993).
Empiric perphenazine applications have been done in 6 individuals of 5 different parrot species combined with various therapies in the Veterinary Department of Al Wabra Wildlife Preservation (AWWP) and Leipzig Zoo.

Case Reports
A 8-year-old, female, hand reared, and human imprinted Gang-Gang Cockatoo (Callocephalon fimbriatum), 230g bodyweight showed severely feather destructive behavior. More than 6 months of conservative treatments, like dietary changes and behavioral enrichment failed. Blood checks for minerals and vitamins did not reveal any deficiencies or intoxications. Pairing or flocking with other birds failed; she even started to pluck her cage mate. Oral treatment with haloperidol was given for more than 4 months (a commonly known sedation drug in parrots with feather plucking (LENNOX and VAN DER HEYDEN, 1993) without significant clinical changes. An initial injection of 2mg perphenazine sc was given. About one hour after injection the bird was very dizzy for 36 hours, but no change in feeding behavior occurred. Feather plucking was reduced. Two month later another injection was given because the bird started plucking again. Another two injections with only one month interval of 0,5mg perphenazine followed until the full plumage was recovered. The bird is in normal plumage until today.
Two 8-month-old Scarlet Macaws (Ara macao) siblings, around 800g bodyweight showed feather plucking maybe imitated from their mother, because the mother is a chronic feather picker. She was not yet treated with perphenazine to avoid disturbance of her breeding behavior. But the two siblings have been treated with a total dosage of 1mg perphenazine sc each. They were very calm for 48 hours, but appetite was not effected. After around two months some feather damaging behavior resumed. Therefore another injection of 1mg perphenazine sc was performed with the same initial signs. Since that time no further plucking was anymore observed.
A 600g, female, Palm Cockatoo (Probosciger aterrimus) showed aggressions towards her male and also destroyed eggs. An 1mg total dose of perphenazine was given with the same effect like in the other species: very calm for around 48 hours, no change of feeding behavior and no aggression for around 1 month. Unfortunately a repeated perphenazine injection to expand the effect by the same dosage failed. 48 hours after the second injection the bird was found dead. Necropsy showed a severe hemorrhagic enteritis with E. coli infection and hepatitis.
A 350g Lilacine Amazon (Amazona autumnalis lilacina) was treated with 1mg perphenazine due to plumage damage on her breast. The reaction was identical to what have been observed in the patients mentioned above. Subsequent diagnostics in this case showed a zinc intoxication (52,2µmol/l serum) and the treatment was changed, because the effect of perphenazine was not indicated any more.
The fifth species was a female Spix’s Macaw (Cyanopsitta spixii). The bird was reported sick, all blood works, and microbiological results were more or less within the normal limits or negative but the bird kept loosing weight and stopped eating. She was force fed various times daily to keep her body weight of 240g. A crop-biopsy gave the diagnosis: positive for PDD (Proventricular Dilatation Disease). After six weeks of force feeding, a perphenazine-injection of 1mg sc was given, immediately she started eating pellets on her own again, even though she showed central nervous signs. Every kind of handling was stopped. Three weeks later she refused eating again, so another 1mg perphenazine-injection was given. After that she was eating again but looked sleepy, as a normal result from the drug, but was still perching. Two days later she was observed still alive, perching, sleepy, holding a pellet. In the following night she died due to the incurable Proventriculus Dilatation Disease.
In all cases we have used an injectable solution of 10mg perphenazine per ml. We diluted 0,1ml of DECENTAN® (100mg Perphenazine/ml) with 0,9ml sterile water.

Results and Discussion
This empiric trial in five different species of psittaciformes showed that subcutaneous injections of perphenazine seems to be safe, at least concerning the clinical symptoms observed after injection. Even the wide dosage range of 1,25 to 8,7mg per kilogram bodyweight used in the trial indicate the drug as useful for treatment in combination with a thorough diagnostic evaluation in each individual case. Of course further research is needed to prove the safety of perphenazine. In our experience perphenazine is helpful in the management of feather damaging behavior, if all other treatments, diagnostics and behaviour enrichment have failed. In those cases one or two injections of perphenazine can be very effective to calm the bird and to give the plumage a chance to recover at least as long as the drug is working. In this context we believe that somehow a “rebooting of the mind” can be initiated, which might last longer than the drug actually works. The main use in humans is the management of psychotic disorders (BALDESSARINI, 1985). In our experience it is advisable to change the cage or the environment of the bird during the treatment with perphenazine to be successful in stopping the feather destructive behavior. Unlike the report of WINTERER & WIESNER (1998), who found that stereotypic behavior in some zoo species could be reserved in the context of reduced activity, but reoccurred with the same intensity after the effect of perphenazine stopped, however environmental changes were not included in this study with zoo species!
The surprising effect in the Spix’s Macaw treatment of appetite stimulus could be explained by the second indication in human medicine for perphenazine: its use for the control of severe nausea and vomiting (UNGEMACH, 2002). Vomiting and dysphagia are common clinical signs of PDD (GREGORY et al., 1994) and the antiemetic effect of perphenazine might give the trigger to start eating again. The improved appetite might also reflect reduced stress from being force fed several times daily and the sedative effect of perphenazine may have relaxed the bird encouraging it to eat.
In the Palm Cockatoo we used the sedative effect of perphenazine to reduce aggression towards the cage mate and hoping to save eggs. The first injection was effective until the drug was metabolized after four weeks. The cause of the sudden death two days after the second injection, most probably caused by the enteritis and the hepatitis or eventually by perphenazine, which is metabolized in the liver, could not be proven afterwards. But it showed very clear that thorough diagnostic evaluation is needed before using it.
Since perphenazine injections, especially the oily long acting formulas, are more potent than oral formulas and even higher dosages are recommended in oral applications, it seems to be the ideal drug for long-term treatments. Only one injection every four to six weeks reduces the stress for the patient and needs no further food formulary. The application of perphenazine is not a complete solution, but might be a very effective support in handling different psychological disorders in psittaciformes, but still it needs great care to use it, because it is not registered for psittaciformes.
It is very important to shake the self-made perphenazine-water-emulsion extremely well and inject it immediately. The use of propylenglycol as an dissolvent should be avoided in birds as it might be toxic for some bird species (RICHIE BW et al., 1999).

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