Folia Psychiatrica et Neurologica Japonica, Vol. 29, No. 3, 1975
Studies on Thyroid Therapy and Thyroid Function in Depressive Patients Takahisa Yamaguchi, M.D., Junichi Nomura, M.D., Mitsuhiro Nishikubo, M.D., Ryotaro Tsujimura, M.D. and Noboru' Hatotani, M.D. Department of Psychiatry, Mie University School of Medicine, Tsu City, Mie Prefecture
INTRODUCTION There are a number of cases of persistent depression which have failed to respond adequately to tricyclic antidepressants and have become refractory over a period of months or even years. In depression, especially in refractory cases, we have often found hypometabolism to be low in terms of basal metabolic rate (BMR). In some of these cases, the administration of a thyroid hormone combined with tricyclic antidepressants dramatically improved the clinical conditions. In this study, we have followed the clinical course of some representative cases of persistent depression which had responded well to the thyroid hormone and have examined the thyroid function in depressive patients. RESULTS 1. Thyroid Therapy of Persistent Depression Case I , F.O., 48-year-old womm (Fig. I )
In December 1970, after her daughter's marriage, F.O. became inert, maudlin and began to feel lonely. Then she gradually became depressed and agitated. She complained of insomnia, loss of appetite, weakness and various hypochondriacal distresses. -
Received for publication June 16, 1975.
She was hospitalized twice and treated with amitriptyline and imipramine with maximum doses of 300 mg/day, but her condition did not improve very much. Her BMR was low (-16%), but her protein bound iodine (PBI, 9.0pg/100 ml), Triosorb (31.3%) and total cholesterol (185 mg/ 100 ml) were within the normal range. Dessicated thyroid was added to the antidepressants with increasing doses from 10mg/day up to 140mg/day. She recovered rapidly and her BMR has maintained the normal range. Case 2, H.T., 27-yecar-old man (Fig. 2 )
In March 1970, H.T. became depressed and complained of low mood, loss of interest, self-depreciation and a feeling of insufficiency. His symptoms were alleviated once by admission to the hospital but he relapsed soon thereafter. In addition to the above symptoms, he complained of depersonalization and impaired concentration. This condition continued unchanged for about a year despite treatment with tricyclic antidepressants. His BMR was low (-22%) and total cholesterol was somewhat high (295 mg/lOO ml). RES-0-MAT TB (1.03) and Tetrasorb (10 pg/lOO ml) were within the normal range. By administering dessicated thyroid (about 100 mg/day), these symptoms disappeared rapidly. He became hypomanic for a while and then recovered completely. After recovery, his BMR (-3 %)
T. Yamaguchi et al.
222
and total cholesterol (193 mg/100 ml) were normal. Case 3, T.S., 25-year-old
cyclic antidepressants (200 mg/day) were administered continuously, he became chronically depressed. Dessicated thyroid (40 mg/ day) reduced his complaints, but he still rem&ned slightly depressed. His BMR was low (-27%). By increasing the dosage of dessicated thyroid up to 100 mg/day, his BMR became normal (+lo%) and he re-
man (Fig. 3)
Since 1966, T.S. had fallen into a depressive state on numerous occasions, during which he complained of sleeplessness, anxiety, irritability and retardation. Although tri-
I-
Psyckic state
-- l 20 o]
Thyrad
hormme
AdlQprm
g
Desiccated thyrad
01 lrnipramine and Arnitript$ine
mgl
200
May Jm JJ
Mar Apr
A@
SeP Oct. Nov Oec J a n Feb Mar Apr
I971
May Jm
J 972
Fig. I : Clinical course of Case 1, F. 0.
Thyrad
B
b m m
0.11
~
Aug
Sep Oct Nov D a c -Jan Feb Mar Apr
I970
May Jm JJ
I971
Fig. 2: Clinical course of Case 2, H. T
Aug Sep Oct Now
Thyroid Therapy and Thyroid Function in Depression covered rapidly. No further depressive phase was observed. Case 4, M.K., 23-year-old w o m n (Fig. 4 )
In 1965, M.K. suffered a spell of hypomanic state and, in 1966, one of a depressive state. In 1967, she became depressed, agitated and retarded. The depressive state
223
continued for nine months despite the administration of antidepressants. Her BMR was very low (-24%, -32%, -16,%), although her PBI was normal (5.5 pg/lOO ml). By the addition of dessicated thyroid (150 mg/day), she recovered very rapidly and her BMR increased to the normal range ( + 5 % , +lo%).
_P+C
state
Jm. Jd. Aug.
Sep.0 c t . N o v . Dee. Jan. Feb.
M a r . Apr. M a y Jm. Jd Aug.
sep. Oct
1971
I970
Fig. 3: Clinical course of Case 3, T. S.
Antt-eSSd
Feb Mar Apr M a y Jm. Jd
I967
Oct. Sep Dec Nov Oec Jan
Feb Mar Apr M a y
I968
Fig. 4: Clinical course of Case 4, M. K.
224
T. Yamaguchi etal.
Case 5 , M.I., 22-year-old womm (Fig. 5 )
In 1967, M.I. delivered her first child. One month after delivery, she became depressed and somewhat perplexed. She cornplained of sleeplessness, agitation, anxiety and hypochondriacal distresses. These symptoms remained unchanged for eight months.
+
m
p s ~ state c
Thyrad
Her BMR (-9%, -1 1%) and PBI (2.9 pg/ 100ml) tended to be low, though her Triosorb was n o I T d (33.3%). Dessicated thyroid (about 150 mg/daY) with thhidazine (75 mg/daY) brought her a rapid recovey with an increase of BMR ( +2 4 %, f 2 3 % , 13%).
g D&ucatec
0.1
thyroid
Thaidazlne Delivery
i, Jan
,
,
,
,
,
,
Feb.Mar Apr. M a y Jm, Jd
,
,
,
,
,
.
,
,
Aug Sep Oct Nov Dec J a n Feb Mar
68
,
Apr
I969
Fig. 5: Clinical course of Case 5 , M. I.
Psychc state
May Jm Jd
1970
Aug Sw Oct Nov Dec Jan
Feb Mar Apr
I971
Fig. 6: Clinical course of Case 6, S . S.
May Jm Jd
Aug
Thyroid Therapy and Thyroid Function in Depression Case 6 , S.S., 46-year-old man (Fig.6 )
In 1970, S.S. became depressed and perplexed, and then fell into a state of confusion with hallucinations and delusions. He recovered from the confusion after electroshock treatments, but remained depressed for three months. His BMR was a little low (-1 1%), though his Triosorb (3 1.3%) and total cholesterol (177 mg/ 100 ml) were normal. Dessicated thyroid (50 mg/day) with antidepressants brought him to rapid recovery. These representative cases, which were refractory to the antidepressants alone, and responded well to the thyroid hormone may be grouped as follows: (1) Long lasting subdepressive states with anxiety, agitation and retardation (Cases 1-4). (2) Persistent depressive states continued from puerperium or followed after acute psychosis (Cases 5 and 6). From the viewpoint of thyroid function, we found it characteristic of these cases that their basal metabolic rates were slightly lower than the normal range or showed low normal values, while other indices, such as Triosorb, Tetrasorb, PBI, total cholesterol and so on, were mostly within the normal range. It was also characteristic that, when thyroid hormones were effective, in spite of long-term medication, the symptoms of hyperthyroidism and/or the excessive increase of BMR were seldom seen. These results require a further examination of the thyroid function of depressed patients, especially of the persistent cases.
2. Thyroid Function of Depressive Patients Serum PBI and the Effect of Thyroid Stimulating Hormone (TSH)
Fifteen normal subjects (seven men and eight women, average age 31) and thirty-five depressed patients (twenty-two men and
225
thirteen women, average age 36) were chosen for the examination. Among the depressed patients, twelve patients (eight men and four women, average age 40) were reexamined after recovery. PBI was determined by the method of Foss et aL8 PBI was measured at 10 a.m. and then 10 U of TSH (Thytropar, Tokyo Tanabe) was injected intramuscularly. At 10 a.m. of the next day, PBI was measured again. Before the injection of TSH, serum PBI standard was 6.1k0.7 pg/lOO ml (mean error) in normal subjects, 5.920.3 pg/lOO ml in depressed patients and 5.4*0.4pg/ 100 ml in recovered patients. There was no significant difference among them. After the injection of TSH, serum PBI was 8.6k0.8 pg/lOO ml in normal subjects, 9.9f0.5 pg/ 100ml in depressed patients and 8.3k0.1 pg/100ml in recovered patients. The increase of PBI was 2.5, 4.0 and 2.9 pg/lOO ml respectively. The increase of PBI was significantly higher (P
Studies on Thyroid Therapy and Thyroid Function in Depressive Patients Takahisa Yamaguchi, M.D., Junichi Nomura, M.D., Mitsuhiro Nishikubo, M.D., Ryotaro Tsujimura, M.D. and Noboru' Hatotani, M.D. Department of Psychiatry, Mie University School of Medicine, Tsu City, Mie Prefecture
INTRODUCTION There are a number of cases of persistent depression which have failed to respond adequately to tricyclic antidepressants and have become refractory over a period of months or even years. In depression, especially in refractory cases, we have often found hypometabolism to be low in terms of basal metabolic rate (BMR). In some of these cases, the administration of a thyroid hormone combined with tricyclic antidepressants dramatically improved the clinical conditions. In this study, we have followed the clinical course of some representative cases of persistent depression which had responded well to the thyroid hormone and have examined the thyroid function in depressive patients. RESULTS 1. Thyroid Therapy of Persistent Depression Case I , F.O., 48-year-old womm (Fig. I )
In December 1970, after her daughter's marriage, F.O. became inert, maudlin and began to feel lonely. Then she gradually became depressed and agitated. She complained of insomnia, loss of appetite, weakness and various hypochondriacal distresses. -
Received for publication June 16, 1975.
She was hospitalized twice and treated with amitriptyline and imipramine with maximum doses of 300 mg/day, but her condition did not improve very much. Her BMR was low (-16%), but her protein bound iodine (PBI, 9.0pg/100 ml), Triosorb (31.3%) and total cholesterol (185 mg/ 100 ml) were within the normal range. Dessicated thyroid was added to the antidepressants with increasing doses from 10mg/day up to 140mg/day. She recovered rapidly and her BMR has maintained the normal range. Case 2, H.T., 27-yecar-old man (Fig. 2 )
In March 1970, H.T. became depressed and complained of low mood, loss of interest, self-depreciation and a feeling of insufficiency. His symptoms were alleviated once by admission to the hospital but he relapsed soon thereafter. In addition to the above symptoms, he complained of depersonalization and impaired concentration. This condition continued unchanged for about a year despite treatment with tricyclic antidepressants. His BMR was low (-22%) and total cholesterol was somewhat high (295 mg/lOO ml). RES-0-MAT TB (1.03) and Tetrasorb (10 pg/lOO ml) were within the normal range. By administering dessicated thyroid (about 100 mg/day), these symptoms disappeared rapidly. He became hypomanic for a while and then recovered completely. After recovery, his BMR (-3 %)
T. Yamaguchi et al.
222
and total cholesterol (193 mg/100 ml) were normal. Case 3, T.S., 25-year-old
cyclic antidepressants (200 mg/day) were administered continuously, he became chronically depressed. Dessicated thyroid (40 mg/ day) reduced his complaints, but he still rem&ned slightly depressed. His BMR was low (-27%). By increasing the dosage of dessicated thyroid up to 100 mg/day, his BMR became normal (+lo%) and he re-
man (Fig. 3)
Since 1966, T.S. had fallen into a depressive state on numerous occasions, during which he complained of sleeplessness, anxiety, irritability and retardation. Although tri-
I-
Psyckic state
-- l 20 o]
Thyrad
hormme
AdlQprm
g
Desiccated thyrad
01 lrnipramine and Arnitript$ine
mgl
200
May Jm JJ
Mar Apr
A@
SeP Oct. Nov Oec J a n Feb Mar Apr
I971
May Jm
J 972
Fig. I : Clinical course of Case 1, F. 0.
Thyrad
B
b m m
0.11
~
Aug
Sep Oct Nov D a c -Jan Feb Mar Apr
I970
May Jm JJ
I971
Fig. 2: Clinical course of Case 2, H. T
Aug Sep Oct Now
Thyroid Therapy and Thyroid Function in Depression covered rapidly. No further depressive phase was observed. Case 4, M.K., 23-year-old w o m n (Fig. 4 )
In 1965, M.K. suffered a spell of hypomanic state and, in 1966, one of a depressive state. In 1967, she became depressed, agitated and retarded. The depressive state
223
continued for nine months despite the administration of antidepressants. Her BMR was very low (-24%, -32%, -16,%), although her PBI was normal (5.5 pg/lOO ml). By the addition of dessicated thyroid (150 mg/day), she recovered very rapidly and her BMR increased to the normal range ( + 5 % , +lo%).
_P+C
state
Jm. Jd. Aug.
Sep.0 c t . N o v . Dee. Jan. Feb.
M a r . Apr. M a y Jm. Jd Aug.
sep. Oct
1971
I970
Fig. 3: Clinical course of Case 3, T. S.
Antt-eSSd
Feb Mar Apr M a y Jm. Jd
I967
Oct. Sep Dec Nov Oec Jan
Feb Mar Apr M a y
I968
Fig. 4: Clinical course of Case 4, M. K.
224
T. Yamaguchi etal.
Case 5 , M.I., 22-year-old womm (Fig. 5 )
In 1967, M.I. delivered her first child. One month after delivery, she became depressed and somewhat perplexed. She cornplained of sleeplessness, agitation, anxiety and hypochondriacal distresses. These symptoms remained unchanged for eight months.
+
m
p s ~ state c
Thyrad
Her BMR (-9%, -1 1%) and PBI (2.9 pg/ 100ml) tended to be low, though her Triosorb was n o I T d (33.3%). Dessicated thyroid (about 150 mg/daY) with thhidazine (75 mg/daY) brought her a rapid recovey with an increase of BMR ( +2 4 %, f 2 3 % , 13%).
g D&ucatec
0.1
thyroid
Thaidazlne Delivery
i, Jan
,
,
,
,
,
,
Feb.Mar Apr. M a y Jm, Jd
,
,
,
,
,
.
,
,
Aug Sep Oct Nov Dec J a n Feb Mar
68
,
Apr
I969
Fig. 5: Clinical course of Case 5 , M. I.
Psychc state
May Jm Jd
1970
Aug Sw Oct Nov Dec Jan
Feb Mar Apr
I971
Fig. 6: Clinical course of Case 6, S . S.
May Jm Jd
Aug
Thyroid Therapy and Thyroid Function in Depression Case 6 , S.S., 46-year-old man (Fig.6 )
In 1970, S.S. became depressed and perplexed, and then fell into a state of confusion with hallucinations and delusions. He recovered from the confusion after electroshock treatments, but remained depressed for three months. His BMR was a little low (-1 1%), though his Triosorb (3 1.3%) and total cholesterol (177 mg/ 100 ml) were normal. Dessicated thyroid (50 mg/day) with antidepressants brought him to rapid recovery. These representative cases, which were refractory to the antidepressants alone, and responded well to the thyroid hormone may be grouped as follows: (1) Long lasting subdepressive states with anxiety, agitation and retardation (Cases 1-4). (2) Persistent depressive states continued from puerperium or followed after acute psychosis (Cases 5 and 6). From the viewpoint of thyroid function, we found it characteristic of these cases that their basal metabolic rates were slightly lower than the normal range or showed low normal values, while other indices, such as Triosorb, Tetrasorb, PBI, total cholesterol and so on, were mostly within the normal range. It was also characteristic that, when thyroid hormones were effective, in spite of long-term medication, the symptoms of hyperthyroidism and/or the excessive increase of BMR were seldom seen. These results require a further examination of the thyroid function of depressed patients, especially of the persistent cases.
2. Thyroid Function of Depressive Patients Serum PBI and the Effect of Thyroid Stimulating Hormone (TSH)
Fifteen normal subjects (seven men and eight women, average age 31) and thirty-five depressed patients (twenty-two men and
225
thirteen women, average age 36) were chosen for the examination. Among the depressed patients, twelve patients (eight men and four women, average age 40) were reexamined after recovery. PBI was determined by the method of Foss et aL8 PBI was measured at 10 a.m. and then 10 U of TSH (Thytropar, Tokyo Tanabe) was injected intramuscularly. At 10 a.m. of the next day, PBI was measured again. Before the injection of TSH, serum PBI standard was 6.1k0.7 pg/lOO ml (mean error) in normal subjects, 5.920.3 pg/lOO ml in depressed patients and 5.4*0.4pg/ 100 ml in recovered patients. There was no significant difference among them. After the injection of TSH, serum PBI was 8.6k0.8 pg/lOO ml in normal subjects, 9.9f0.5 pg/ 100ml in depressed patients and 8.3k0.1 pg/100ml in recovered patients. The increase of PBI was 2.5, 4.0 and 2.9 pg/lOO ml respectively. The increase of PBI was significantly higher (P
