0
Get Alert
Please Wait... Processing your request... Please Wait.
You must sign in to sign-up for alerts.

Please confirm that your email address is correct, so you can successfully receive this alert.

1
Letter to the Editor   |    
Galantamine for Treatment-Resistant Schizophrenia
TRINA B. ALLEN, M.D.; JOSEPH P. McEVOY, M.D.
Am J Psychiatry 2002;159:1244-1245. doi:10.1176/appi.ajp.159.7.1244

To the Editor: Abnormal neurotransmission at nicotinic cholinergic receptors may contribute to the pathophysiology of schizophrenia (1). Clozapine may favorably affect these abnormal nicotinic mechanisms (2). We report here on two treatment-resistant patients with schizophrenia whose successful treatment with clozapine had been discontinued because of agranulocytosis. Both fared poorly while taking other antipsychotics. Both showed therapeutic benefit when galantamine, a noncompetitive agonist/allosteric modulator at nicotinic cholinergic receptors (3), was added to their treatment with risperidone.

Mr. A was a 28-year-old man with persistent auditory hallucinations and persecutory delusions who had been given repeated placement in the community, but these efforts had failed because of frequent episodes of agitation, threatening behavior, and destruction of property that seemed to be driven by paranoia and his hearing "voices." Galantamine was introduced and brought to an oral dose of 8 mg b.i.d. over 2 weeks. The episodes of agitation disappeared, and Mr. A became more capable of sustained routine conversation in which he could rationally evaluate his psychopathology. After an additional 2 weeks of treatment, he was successfully placed in a group home, where he has continued to do well for 2 months.

Mr. B was a 53-year-old man with profoundly disorganized thoughts and poor self-care, including wearing multiple layers of clothing inside out and backward. He repeatedly wandered away from the group home where he had been placed. Galantamine treatment was initiated and brought to an oral dose of 12 mg b.i.d. Mr. B’s thoughts became more organized. He wore his clothes correctly and was more social with staff and other patients. Staff at the group home report that since returning there, he no longer wanders away and, in fact, signs out when taking local walks. He remains more social and has maintained clearly improved dressing and hygiene.

The active components of risperidone and galantamine exhibit no change in their bioavailabilities when co-administered (4). Galantamine alters the structure of nicotinic receptors, making them more receptive to nicotinic agonists, in addition to inhibiting the breakdown of acetylcholine by its cholinesterase (5).

Controlled double-blind trials of galantamine as an adjunctive treatment for schizophrenia are currently underway. These two patients were both very heavy smokers and had shown a favorable therapeutic response to clozapine that could not be matched by treatment with any other currently available antipsychotic. Both of these attributes (smoking and clozapine response) may signal that nicotinic pathophysiology contributed to their illnesses and that an agent such as galantamine that can augment nicotinic function may be a useful treatment (6).

Adler LE, Olincy A, Waldo M, Harris JG, Griffith J, Stevens K, Flach K, Nagamoto H, Bickford P, Leonard S, Freedman R: Schizophrenia, sensory gating, and nicotinic receptors. Schizophr Bull  1998; 24:189-202
[PubMed]
[CrossRef]
 
Nagamoto HT, Adler LE, Hea RA, Griffith JM, McRae KA, Freedman R: Gating of auditory P50 in schizophrenia: unique effects of clozapine. Biol Psychiatry  1996; 40:181-188
[PubMed]
[CrossRef]
 
Maelicke A, Albuquerque EX: Allosteric modulation of nicotinic acetylcholine receptors as a treatment strategy for Alzheimer’s disease. Eur J Pharmacol  2000; 393:165-170
[PubMed]
[CrossRef]
 
Huang F, Lasseter KL, Janssens L, Verhaeghe T, Lau H, Zhao Q: Pharmacokinetic and safety assessments of galantamine and risperidone after the two drugs were administered alone and together. J Clin Pharmacol (in press)
 
Arias HR: Localization of agonist and competitive antagonist binding sites on nicotinic acetylcholine receptors. Neurochem Int 2000: 36:595-645
 
McEvoy JP, Freudenreich O, Wilson WH: Smoking and therapeutic response to clozapine in patients with schizophrenia. Biol Psychiatry  1999; 46:125-129
[PubMed]
[CrossRef]
 
+

References

Adler LE, Olincy A, Waldo M, Harris JG, Griffith J, Stevens K, Flach K, Nagamoto H, Bickford P, Leonard S, Freedman R: Schizophrenia, sensory gating, and nicotinic receptors. Schizophr Bull  1998; 24:189-202
[PubMed]
[CrossRef]
 
Nagamoto HT, Adler LE, Hea RA, Griffith JM, McRae KA, Freedman R: Gating of auditory P50 in schizophrenia: unique effects of clozapine. Biol Psychiatry  1996; 40:181-188
[PubMed]
[CrossRef]
 
Maelicke A, Albuquerque EX: Allosteric modulation of nicotinic acetylcholine receptors as a treatment strategy for Alzheimer’s disease. Eur J Pharmacol  2000; 393:165-170
[PubMed]
[CrossRef]
 
Huang F, Lasseter KL, Janssens L, Verhaeghe T, Lau H, Zhao Q: Pharmacokinetic and safety assessments of galantamine and risperidone after the two drugs were administered alone and together. J Clin Pharmacol (in press)
 
Arias HR: Localization of agonist and competitive antagonist binding sites on nicotinic acetylcholine receptors. Neurochem Int 2000: 36:595-645
 
McEvoy JP, Freudenreich O, Wilson WH: Smoking and therapeutic response to clozapine in patients with schizophrenia. Biol Psychiatry  1999; 46:125-129
[PubMed]
[CrossRef]
 
+
+

CME Activity

There is currently no quiz available for this resource. Please click here to go to the CME page to find another.
Submit a Comments
Please read the other comments before you post yours. Contributors must reveal any conflict of interest.
Comments are moderated and will appear on the site at the discertion of APA editorial staff.

* = Required Field
(if multiple authors, separate names by comma)
Example: John Doe



Web of Science® Times Cited: 40

Related Content
Books
What Your Patients Need to Know About Psychiatric Medications, 2nd Edition > Chapter 77.  >
APA Practice Guidelines > Chapter 16.  >
The American Psychiatric Publishing Textbook of Psychopharmacology, 4th Edition > Chapter 41.  >
The American Psychiatric Publishing Textbook of Psychopharmacology, 4th Edition > Chapter 41.  >
Topic Collections
Psychiatric News
PubMed Articles