Lithium in the Treatment of Schizophrenia and Schizoaffective Disorders Robert J.
Prien, PhD
has been used in the treatment of schizophrenic and schizoaffective disorders with inconclusive results. Interpretation of the results has been limited either by inadequate sample sizes or by the scarcity of adequately controlled trials. An additional problem in interpreting studies of the therapeutic use of lithium in schizoaffective disorders arises from the lack of universally accepted criteria for classifying such disorders at the time of the study.
presence or absence of affective symptomatology. Van Kämmen and DeFraites" emphasize that even stud¬ ies that report antipsychotic action with lithium do not claim that lithium is more effective than a properly selected neuroleptic. Clearly, neuroleptic drugs remain the medication of choice for the treatment of schizophrenia. It has been suggested, however, that schizophrenics who do not respond optimally to neuroleptic therapy may benefit from the combination of lithium and a neuroleptic.'""'-
SCHIZOPHRENIA
SCHIZOAFFECTIVE DISORDERS
In general, there are three prevailing opinions regarding the efficacy of lithium in schizophrenia: 1. Lithium is not effective in schizophrenia and may actually be deleterious because of the increased susceptibility of schizophrenics to lithium-induced CNS toxicity.1-3 2. Schizophrenic patients who respond to lithium treatment are in reality "atypical" manic-depressives. Since severe mania may mimic schizophrenia (including appearance of first-rank Schneiderian symptoms), a favorable response to lithium indicates a need for rediagnosis.4-6 3. There is a subgroup of "pure" schizophrenics who respond positively to lithium.7-9 Overall, the studies evaluating effectiveness of lithium in schizophrenia do not have adequate sample size or sufficient controls to judge the relative merits of the aforementioned positions. In most studies, interpretation is further limited by vaguely defined diagnostic criteria, with little emphasis placed on diagnostic subtype or the
There are three prevailing opinions regarding the effica¬ cy of lithium in the treatment of schizoaffective illness: (1) lithium is effective against pathological excitement in schizoaffective illness but has no affect on schizophrenic behavior""'7'; (2) lithium is effective with both the affective and schizophrenic components of schizoaffective psycho¬ sis7"3"'8; and (3) lithium is ineffective with both affective and schizophrenic behavior.'" Results tend to favor the first alternative; the prevailing opinion is that the more predominant the affective component, the more effective the lithium therapy. However, the evidence is not entirely conclusive. Studies also suggest that lithium is beneficial in preventing schizoaffective recurrences.'7-""' These find¬ ings also require further confirmation. A major problem in interpreting lithium studies in schizoaffective illness is the scarcity of controlled trials comparing lithium with placebo and neuroleptic drugs. Two trials comparing lithium carbonate with chlorproma¬ zine in excited schizoaffective illness provide contradictory findings.18 '" (A further discussion of this is found in the article by Goodwin and Zis, 840 this issue.)
Lithium
From the Psychopharmacology Research Branch, National Institute of Mental Health, Rockville, Md.
Downloaded From: http://archpsyc.jamanetwork.com/ by a La Trobe University User on 05/25/2016
A more frustrating problem affecting interpretation of therapeutic studies in schizoaffective illness is that at the time the studies were done, there was no standardized system for classifying the disorder. Schizoaffective illness has been alternately described as a subtype of schizophrenia,2-îa a form of affective disor¬ der,-4 a third psychosis different from both manic- "'
depressive illness
and schizophrenia,-'"2T and a genuine mixed-state intermediate on the continuum from pure affective illness to pure schizophrenia.28-29 The recently developed Research Diagnostic Criteria (RDC)3" for schizoaffective illness should contribute to the resolution of these questions.—Ed.
References 1. Schou
M, Juel-Nielsen N, Stromgren E,
et al: The treatment of manic
psychosis by the administration of lithium salts. J Neurol Neurosurg Psychiatry 17:250-260, 1954. 2. Gerbino L, Oleshanky M, Gershon S: Clinical use and mode of action of lithium, in Lipton MA, DiMascio A, Killam KF (eds): Psychopharmacology: A Generation of Progress. New York, Raven Press, 1978, pp 1261-1275. 3. Shopsin B, Kim SS, Gershon S: A controlled study of lithium versus chlorpromazine in acute schizophrenics. Br J Psychiatry 119:435-440, 1971. 4. Abrams R, Taylor MA, Gaztanaga P: Manic-depressive illness and
paranoid schizophrenia: A phenomenologic, family history, response study. Arch Gen Psychiatry 31:640-642, 1974. 5.
Carpenter WT, Strauss JS, Muleh S:
Are there
and treatment-
pathognomonic signs in
An empiric investigation of Schneider's first-rank symptoms. Arch Gen Psychiatry 28:847-852, 1973. 6. Rapps MS, Edwards P: A high prevalence of affective disorders discovered in a schizophrenia clinic. Can Psychiatr Assoc J 22:181-183, 1977. 7. Glesinger B: Evaluation of lithium in treatment of psychotic excitement. Med J Aust 41:277-283, 1954. 8. Taheri A: Lithium in schizophrenia. Am J Psychiatry 133:1208, 1976. 9. Van Kammen DP, DeFraites EG: Lithium in schizophrenia, in Cooper TB, Gershon S, Kline N, et al (eds): Lithium: Controversies and Unresolved Issues. Amsterdam, Excerpta Medica, to be published. 10. Meiers RL: Lithium carbonate as an adjunct in the treatment of schizophrenia. Schizophrenia Bull 2:87-91, 1970. 11. Small JG, Kellams JJ, Milstein V, et al: A placebo-controlled study of lithium combined with neuroleptics in chronic schizophrenic patients. Am J
schizophrenia?
Psychiatry 132:1315-1317, 1975. 12. Van Putten T, Sanders DG: Lithium Ment Dis 161:255-265, 1975.
in treatment failure. J Nerv
13. Gottfries CG: Effect of lithium salts on various kinds of psychiatric disorders. Acta Psychiatr Scand 203(suppl):157-167, 1964. 14. Rice D: Use of lithium salts in the treatment of amanic states. J Ment Sci 102:604-611, 1956. 15. Zall H, Therman PG, Myers JM: Lithium carbonate: A clinical study. Am J Psychiatry 125:549-555, 1968.
16. Mosketts
KV, Bel'skaya GM, Muratova ID: Experience in the
iodinated lithium in the treatment of
some
use
of
psychotic states. Zh Nevropatol
Psikhiatr 63:92-95, 1963. 17. Perris C: Morbidity suppressive effect of lithium carbonate in cycloid psychosis. Arch Gen Psychiatry 35:328-331, 1978. 18. Prien RF, Caffey EM, Klett CJ: A comparison of lithium carbonate and chlorpromazine in the treatment of excited schizoaffectives: Report of the Veterans Administration and National Institute of Mental Health Collaborative Study Group. Arch Gen Psychiatry 27:182-189, 1972. 19. Johnson G: Differential response to lithium carbonate in manicdepressive and schizoaffective disorders. Dis Nerv Syst 31:613-615, 1970. 20. Angst J, Weiss P, Grof P, et al: Lithium prophylaxis in recurrent affective disorders. Br J Psychiatry 116:604-613, 1970. 21. Smulevitch AB, Zavidovskaya AL, Igonin AL, et al: The effectiveness of lithium in affective and schizoaffective psychoses. Br J Psychiatry 125:65-72, 1974. 22. Bleuler E: A Textbook of Psychiatry. New York, Macmillan Co, 1924. 23. American Psychiatric Association Committee on Nomenclature and Statistics: Diagnostic and Statistical Manual of Mental Disorders, ed 2. Washington, DC, American Psychiatric Association, 1968. 24. Clayton PJ, Rodin L, Winokur G: Family history studies: III. Schizoaffective disorder, clinical and genetic factors including a one to two year follow-up. Compr Psychiatry 9:31-49, 1968. 25. Hoch P, Rachlin HL: An evaluation of manic-depressive psychosis in the light of follow-up studies. Am J Psychiatry 97:831-843, 1941. 26. Eitinger L, Lane CL, Langfelt G: The prognostic value of the clinical picture and the therapeutic value of physical treatment in schizophrenia and the schizophreniform states. Acta Psychiatr Neurol Scand 33:33-53, 1958. 27. Mitsuda H: Concept of atypical psychosis from the aspect of clinical genetics. Acta Psychiatr Scand 41:373-377, 1965. 28. Beck AT: Depression: Clinical, Experimental, and Theoretical Aspects. New York, Harper & Row Publishers Inc, 1969. 29. Post F: Schizoaffective symptomatology in late life. Br J Psychiatry 118:437-445, 1971. 30. Spitzer RL, Endicott J, Robins E: Research Diagnostic Criteria: Rationale and reliability. Arch Gen Psychiatry 35:773-782, 1978.
Downloaded From: http://archpsyc.jamanetwork.com/ by a La Trobe University User on 05/25/2016
Prien, PhD
has been used in the treatment of schizophrenic and schizoaffective disorders with inconclusive results. Interpretation of the results has been limited either by inadequate sample sizes or by the scarcity of adequately controlled trials. An additional problem in interpreting studies of the therapeutic use of lithium in schizoaffective disorders arises from the lack of universally accepted criteria for classifying such disorders at the time of the study.
presence or absence of affective symptomatology. Van Kämmen and DeFraites" emphasize that even stud¬ ies that report antipsychotic action with lithium do not claim that lithium is more effective than a properly selected neuroleptic. Clearly, neuroleptic drugs remain the medication of choice for the treatment of schizophrenia. It has been suggested, however, that schizophrenics who do not respond optimally to neuroleptic therapy may benefit from the combination of lithium and a neuroleptic.'""'-
SCHIZOPHRENIA
SCHIZOAFFECTIVE DISORDERS
In general, there are three prevailing opinions regarding the efficacy of lithium in schizophrenia: 1. Lithium is not effective in schizophrenia and may actually be deleterious because of the increased susceptibility of schizophrenics to lithium-induced CNS toxicity.1-3 2. Schizophrenic patients who respond to lithium treatment are in reality "atypical" manic-depressives. Since severe mania may mimic schizophrenia (including appearance of first-rank Schneiderian symptoms), a favorable response to lithium indicates a need for rediagnosis.4-6 3. There is a subgroup of "pure" schizophrenics who respond positively to lithium.7-9 Overall, the studies evaluating effectiveness of lithium in schizophrenia do not have adequate sample size or sufficient controls to judge the relative merits of the aforementioned positions. In most studies, interpretation is further limited by vaguely defined diagnostic criteria, with little emphasis placed on diagnostic subtype or the
There are three prevailing opinions regarding the effica¬ cy of lithium in the treatment of schizoaffective illness: (1) lithium is effective against pathological excitement in schizoaffective illness but has no affect on schizophrenic behavior""'7'; (2) lithium is effective with both the affective and schizophrenic components of schizoaffective psycho¬ sis7"3"'8; and (3) lithium is ineffective with both affective and schizophrenic behavior.'" Results tend to favor the first alternative; the prevailing opinion is that the more predominant the affective component, the more effective the lithium therapy. However, the evidence is not entirely conclusive. Studies also suggest that lithium is beneficial in preventing schizoaffective recurrences.'7-""' These find¬ ings also require further confirmation. A major problem in interpreting lithium studies in schizoaffective illness is the scarcity of controlled trials comparing lithium with placebo and neuroleptic drugs. Two trials comparing lithium carbonate with chlorproma¬ zine in excited schizoaffective illness provide contradictory findings.18 '" (A further discussion of this is found in the article by Goodwin and Zis, 840 this issue.)
Lithium
From the Psychopharmacology Research Branch, National Institute of Mental Health, Rockville, Md.
Downloaded From: http://archpsyc.jamanetwork.com/ by a La Trobe University User on 05/25/2016
A more frustrating problem affecting interpretation of therapeutic studies in schizoaffective illness is that at the time the studies were done, there was no standardized system for classifying the disorder. Schizoaffective illness has been alternately described as a subtype of schizophrenia,2-îa a form of affective disor¬ der,-4 a third psychosis different from both manic- "'
depressive illness
and schizophrenia,-'"2T and a genuine mixed-state intermediate on the continuum from pure affective illness to pure schizophrenia.28-29 The recently developed Research Diagnostic Criteria (RDC)3" for schizoaffective illness should contribute to the resolution of these questions.—Ed.
References 1. Schou
M, Juel-Nielsen N, Stromgren E,
et al: The treatment of manic
psychosis by the administration of lithium salts. J Neurol Neurosurg Psychiatry 17:250-260, 1954. 2. Gerbino L, Oleshanky M, Gershon S: Clinical use and mode of action of lithium, in Lipton MA, DiMascio A, Killam KF (eds): Psychopharmacology: A Generation of Progress. New York, Raven Press, 1978, pp 1261-1275. 3. Shopsin B, Kim SS, Gershon S: A controlled study of lithium versus chlorpromazine in acute schizophrenics. Br J Psychiatry 119:435-440, 1971. 4. Abrams R, Taylor MA, Gaztanaga P: Manic-depressive illness and
paranoid schizophrenia: A phenomenologic, family history, response study. Arch Gen Psychiatry 31:640-642, 1974. 5.
Carpenter WT, Strauss JS, Muleh S:
Are there
and treatment-
pathognomonic signs in
An empiric investigation of Schneider's first-rank symptoms. Arch Gen Psychiatry 28:847-852, 1973. 6. Rapps MS, Edwards P: A high prevalence of affective disorders discovered in a schizophrenia clinic. Can Psychiatr Assoc J 22:181-183, 1977. 7. Glesinger B: Evaluation of lithium in treatment of psychotic excitement. Med J Aust 41:277-283, 1954. 8. Taheri A: Lithium in schizophrenia. Am J Psychiatry 133:1208, 1976. 9. Van Kammen DP, DeFraites EG: Lithium in schizophrenia, in Cooper TB, Gershon S, Kline N, et al (eds): Lithium: Controversies and Unresolved Issues. Amsterdam, Excerpta Medica, to be published. 10. Meiers RL: Lithium carbonate as an adjunct in the treatment of schizophrenia. Schizophrenia Bull 2:87-91, 1970. 11. Small JG, Kellams JJ, Milstein V, et al: A placebo-controlled study of lithium combined with neuroleptics in chronic schizophrenic patients. Am J
schizophrenia?
Psychiatry 132:1315-1317, 1975. 12. Van Putten T, Sanders DG: Lithium Ment Dis 161:255-265, 1975.
in treatment failure. J Nerv
13. Gottfries CG: Effect of lithium salts on various kinds of psychiatric disorders. Acta Psychiatr Scand 203(suppl):157-167, 1964. 14. Rice D: Use of lithium salts in the treatment of amanic states. J Ment Sci 102:604-611, 1956. 15. Zall H, Therman PG, Myers JM: Lithium carbonate: A clinical study. Am J Psychiatry 125:549-555, 1968.
16. Mosketts
KV, Bel'skaya GM, Muratova ID: Experience in the
iodinated lithium in the treatment of
some
use
of
psychotic states. Zh Nevropatol
Psikhiatr 63:92-95, 1963. 17. Perris C: Morbidity suppressive effect of lithium carbonate in cycloid psychosis. Arch Gen Psychiatry 35:328-331, 1978. 18. Prien RF, Caffey EM, Klett CJ: A comparison of lithium carbonate and chlorpromazine in the treatment of excited schizoaffectives: Report of the Veterans Administration and National Institute of Mental Health Collaborative Study Group. Arch Gen Psychiatry 27:182-189, 1972. 19. Johnson G: Differential response to lithium carbonate in manicdepressive and schizoaffective disorders. Dis Nerv Syst 31:613-615, 1970. 20. Angst J, Weiss P, Grof P, et al: Lithium prophylaxis in recurrent affective disorders. Br J Psychiatry 116:604-613, 1970. 21. Smulevitch AB, Zavidovskaya AL, Igonin AL, et al: The effectiveness of lithium in affective and schizoaffective psychoses. Br J Psychiatry 125:65-72, 1974. 22. Bleuler E: A Textbook of Psychiatry. New York, Macmillan Co, 1924. 23. American Psychiatric Association Committee on Nomenclature and Statistics: Diagnostic and Statistical Manual of Mental Disorders, ed 2. Washington, DC, American Psychiatric Association, 1968. 24. Clayton PJ, Rodin L, Winokur G: Family history studies: III. Schizoaffective disorder, clinical and genetic factors including a one to two year follow-up. Compr Psychiatry 9:31-49, 1968. 25. Hoch P, Rachlin HL: An evaluation of manic-depressive psychosis in the light of follow-up studies. Am J Psychiatry 97:831-843, 1941. 26. Eitinger L, Lane CL, Langfelt G: The prognostic value of the clinical picture and the therapeutic value of physical treatment in schizophrenia and the schizophreniform states. Acta Psychiatr Neurol Scand 33:33-53, 1958. 27. Mitsuda H: Concept of atypical psychosis from the aspect of clinical genetics. Acta Psychiatr Scand 41:373-377, 1965. 28. Beck AT: Depression: Clinical, Experimental, and Theoretical Aspects. New York, Harper & Row Publishers Inc, 1969. 29. Post F: Schizoaffective symptomatology in late life. Br J Psychiatry 118:437-445, 1971. 30. Spitzer RL, Endicott J, Robins E: Research Diagnostic Criteria: Rationale and reliability. Arch Gen Psychiatry 35:773-782, 1978.
Downloaded From: http://archpsyc.jamanetwork.com/ by a La Trobe University User on 05/25/2016
