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Keywords:

  • clonazepam;
  • essential drug selection;
  • GDS-15;
  • medical care;
  • primary-care physician;
  • psychiatrist;
  • senile depression

Abstract

  1. Top of page
  2. Abstract
  3. INTRODUCTION
  4. CASE AND DISCUSSION
  5. REFERENCES

The patient, a 77-year-old man, was diagnosed with senile depression. He was also diagnosed with depression at other hospitals, and pharmacotherapy by antidepressants was carried out. He was given sulpiride, selective serotonin reuptake inhibitors, a serotonin-norepinephrine reuptake inhibitor, an atypical antidepressant, and tricyclic and tetracyclic antidepressants, but conventional pharmacotherapies using these antidepressant drugs did not alleviate his symptoms. The patient was then administered 0.5 mg/day of clonazepam at bed time. Following 2 weeks of administration, his symptoms were alleviated. The dosage of clonazepam was increased to 0.75 mg/day and remission was facilitated. Four weeks later, the patient displayed further alleviation of his depressive symptoms, so he has been continued on 0.75 mg/day of clonazepam. Essential drug selections for senile depression includes selective serotonin reuptake inhibitors, serotonin-norepinephrine reuptake inhibitors, and atypical antidepressants, but when these are ineffective, tricyclic antidepressants or tetracyclic antidepressants are alternatively selected. When a patient’s symptoms are not alleviated by essential drug selection, as occurred in the current case, clonazepam is considered to be another therapeutic candidate. If they fail to alleviate symptoms, however, then early referral to a specialist is crucial. Enhancing primary-care physicians’ understanding of senile depression and coordination with specialists is essential in the medical care of elderly patients with depression.


INTRODUCTION

  1. Top of page
  2. Abstract
  3. INTRODUCTION
  4. CASE AND DISCUSSION
  5. REFERENCES

Most elderly patients consult a primary-care physician or family doctor because they tend to attribute their symptoms to physical illnesses.1,2 Adequate therapeutic intervention by primary-care physicians is important in the treatment of senile depression.

We report herein the case of an elderly depressive patient, which demonstrates the importance of cooperation between psychiatrist and primary-care physicians, and which also shows the early stage treatment of senile depression.1

CASE AND DISCUSSION

  1. Top of page
  2. Abstract
  3. INTRODUCTION
  4. CASE AND DISCUSSION
  5. REFERENCES

Case

The patient was a 77 year-old man with no reported history of depression whose chief complaints were moodiness, suicidality and difficulty falling asleep.

History of the present illness

The patient was treated for dental pain by Dentist A on 16 January, year X, and was diagnosed with pulpitis. Surgery was needed, so the patient was admitted to Hospital B for dental surgery on 30 January, year X, and discharged a week later. Afterwards, the patient was treated on an outpatient basis, but the intense dental pain manifested again, so the patient was readmitted on 27 February, year X. While in the hospital, the patient had difficulty falling asleep, and was only able to sleep about 2 h per day. Brotizolam was prescribed but had no effect, so triazolam was prescribed. However, the patient continued to have difficulty falling asleep. He was unable to enjoy a sound sleep and his insomnia was prolonged. The patient was discharged on 8 March, year X, but moodiness, inhibition of thought, diminished motivation, loss of appetite, anxiety and irritability manifested in addition to difficulty falling asleep, so the patient was seen at the C Hospital of Internal Medicine on March 16, year X. The patient’s appetite improved somewhat with sulpiride, but alleviation of other symptoms was not seen. The selective serotonin reuptake inhibitors (SSRI) fluvoxamine and paroxetine, the serotonin-norepinephrine reuptake inhibitor (SNRI) milnacipran, the tetracyclic antidepressant mianserin, the atypical antidepressant trazodone, and the tricyclic antidepressants imipramine and clomipramine were used, but had no effect. The quantities of each maximal use of these medicine were: fluvoxamine, 150 mg; paroxetine, 40 mg; milnacipran, 75 mg; mianserin, 60 mg. These applied medicines were ineffective so far as we could determine based on the patient’s reports. Weight loss then occurred and the patient showed a desire to die; on 1 July, year X, he injured himself with a paring knife he had obtained from the kitchen. Afterwards, he repeatedly expressed a desire to die. Worried, his family brought the patient in, where he was first seen by D hospital on 3 July, year X.

Course

The patient complained that the medication prescribed by a previous physician was having no effect, and he had discontinued taking the medication several days prior to his suicide attempt. Upon initial exam, animation in mood and behavior were poor. The patient’s symptoms of difficulty falling asleep, moodiness, inhibition of thought, diminished motivation, loss of appetite, weight loss, anxiety, irritability and suicidality persisted, all of which had an impact on his daily activities, and the patient had been staying indoors. The patient’s GDS-15 (Geriatric Depression Scale) score was 12 points and his HDS-R (Revised Hasegawa Dementia Scale) score was 27 points; nothing remarkable was seen in brain computed tomography (CT), electroencephalography (EEG) or blood and urine tests. The patient was diagnosed with senile depression classified by DSM-IV.3 Because the varied sulpiride, SSRI, SNRI, atypical antidepressants, and tricyclic and tetracyclic antidepressants administered by the previous physician had no effect, the fact that he would be administered medication not originally intended for depression was explained verbally to the patient. After consent was obtained, the patient was administered with clonazepam 0.5 mg/day at v.d.s; this drug is an anticonvulsant with antidepressant and anxiolytic action. Following 2 weeks of administration, the aforementioned symptoms were alleviated and the patient’s GDS-15 score was 7 points, so clonazepam was increased to 0.75 mg/day and remission was facilitated. As an outpatient 4 weeks later, the patient’s GDS-15 score was 1 point and he displayed further alleviation of depressive symptoms. He is currently taking 0.75 mg/day of clonazepam (Table 1).

Table 1.  Depressive symptoms displayed after use of clonazepam
Week (Clonazepam, mg/d)0 (Clonazepam, 0.5)2 (Clonazepam, 0.75)6 (Clonazepam, 0.75)
  1. (+++, severe; ++, moderate; +, mild; ±, minimal; –, none).

GDS-15 (point)1271
Falling asleep+++
Moodiness+++±
Inhibition of thought+++±
Diminished motivation++±
Loss of appetite++
Anxiety+++±
Suicidality persisted+++

Drug therapy for senile depression

Essential treatment strategies for senile depression are no different from those for general depression. When administering medication, attention should be paid to keeping adverse effects to a minimum by starting with small doses of an antidepressant and gradually increasing the dosage; as a guide, doses should be half the amount given to a normal healthy adult.4 This is because drug concentrations in the blood readily rise, and a decline in the rate of drug metabolism by the liver and a decline in hypofiltration by the kidney are quite likely to be present due to the effects of advanced age.4

Recent essential drug selection for senile depression includes the SSRI fluvoxamine and paroxetine, the SNRI milnacipran, and the atypical antidepressant trazodone, but when these are ineffective, tricyclic antidepressants or tetracyclic antidepressants are selected. However, patients whose symptoms are not alleviated by such essential drug selections, as in the current case, are seen frequently. In such instances, excessive anxiety and hypochondria are noted with senile depression in addition to depression and insomnia, so clonazepam, an anticonvulsant with antidepressant and anxiolytic action and moderate sedative action, which is said to have few adverse effects and relatively rapid onset of drug action, is efficacious.5 As an example, Londborg et al. reported that clonazepam alleviated anxiety, sleep disturbance and core symptoms of depression.5 A detailed study reported that low-dose cotherapy of fluoxetine with clonazepam was safe and accelerated the response over 21 days of treatment, decreasing symptomatic anxiety and sleep disturbance and partially suppressing them as SSRI side-effects; it also modestly reduced core symptoms of low mood and loss of interest. Clonazepam is an unique high-potency 1,4-benzodiazepine derivative.6 It has been proposed that its actions are not only mediated at the gamma-aminobutyric acid-sub (A) (GABA-sub (A)) receptor,7 but also due to a modulation of central 5-hydroxytryptamine (5-HT, serotonin) metabolism.8 Clonazepam has been approved by the US Food and Drug Administration (FDA) since 1976 as an antiepileptic drug for the following types of seizures: absence, infantile spasm, atypical absence, myoclonic and atonic.9 It is also used for the treatment of panic disorder and has shown efficacy in case series and in a controlled trial for the acute treatment of mania.10–14

Clonazepam’s long half-life of 20–80 h might render this compound especially promising as a maintenance medication in affective disorder,15 because interdose fluctuation in mood state should be reduced and because it might diminish the likelihood or severity of rebound worsening of symptoms following the discontinuation of augmention.16,17 As a result of administering clonazepam in 100 cases of prolonged depression, Morishita reported that although a dose of clonazepam of 3.0 mg/day is recommended, a high response rate was indicated with clonazepam given at doses of 0.5–3.0 mg/day.18 Thus when using clonazepam in the elderly, in whom drug doses should start with small amounts, doses should start at about 0.5 mg/day and be gradually increased if necessary. In addition, clonazepam enhances the action of SSRI, so concomitant use with SSRI is a good treatment selection for depressive illness.5

Senile depression treatment strategy for primary-care physicians

The elderly, who primarily visit their primary-care physician for physical conditions, may become depressed as a result of mental burdens, and primary-care physicians should treat both physical and mental conditions together. In the treatment of senile depression, the selection of clonazepam and essential drugs such as SSRI and SNRI could be considered. If they fail to alleviate the problem, then early referral to a specialist is vital. Enhancing primary-care physicians’ understanding of senile depression and enhancing coordination with specialists is essential in medical care.

Finally, essential drug selection for senile depression includes SSRI, SNRI, atypical antidepressants, tricyclic antidepressants and tetracyclic antidepressants. When these drugs are ineffective, clonazepam is one candidate to be selected. In this context, we propose possible guidelines for drug selection in the treatment of senile depression as shown in Table 2.2,19

Table 2.  Possible drug selection for elderly depressive patients
I. Moodiness, feeling sad, despair, emotional dejection: Paroxetine, fluvoxamine, milnacipran, nortoripuchirine, clonazepam
II. Anxiety, irritability, restlessness: Paroxetine, fluvoxamine, mianserine, sechipuchirine, trazodone, mapurochirine, clonazepam
III. Diminished motivation, inhibition, no impression: Milnacipran, nortoripuchirine, amokisapine, fluvoxamine, sulpiride, clonazepam
IV. Depression with physical symptoms and dysfunction of automatic nervous system: Sulpiride, fluvoxamine, sechipuchirine, mianserine, mapurochirine, clonazepam

REFERENCES

  1. Top of page
  2. Abstract
  3. INTRODUCTION
  4. CASE AND DISCUSSION
  5. REFERENCES
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    Londborg PD, Smith WT, Glaudin V et al. Short-term cotherapy with clonazepam and fiuoxetine: anxiety, sleep disturbance and core symptoms of depression. J Affect Disord 2000; 61: 7379.
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    Valenca AM, Nardi AE, Nascimento I et al. Double-blind clonazepam vs placebo in panic disorder treatment. Arq Neuropsiquiatr 2000; 58: 10251029.
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    Worthington JJ, Pollack MH, Otto MW et al. Long-term experience with clonazepam in patients with a primary diagnosis of panic disorder. Psychopharmacol Bull 1998; 34: 199205.
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    Adler LW. Mixed bipolar disorders responsive to lithium and clonazepam. J Clin Psychiatry 1986; 47: 4950.
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    Shirakawa O. [The fact of pharmacotherapy of senile depression.] Geriatric Med 2002; 40: 451459. (In Japanese.)