Management of the Office Patient With Anxiety and Depression

Management of the Office Patient With Anxiety and Depression ROBERT

S. WARNER, M.D.

• In this day and age, patients seem to react to environmental, situational and disease-induced stress more readily than in earlier times. Environmental pressures produce anxiety, tension, and depression, together with lethargy, increased irritability and frequently conversion reactions of varying degrees. Acute situational stress provokes a variety of similar symptoms, of which anxiety and tension are most prominent. The patient's reaction to a disease 'process is usually manifested by anxiety, tension and depression, and the symptoms of the primary disease often are accentuated. Even after optimum response to treatment of the underlying condition, the patient may continue to experience extreme discomfort because of his emotional symptoms. The physician usually can do little or nothing to change the unhappy environment or alter the unfortunate situation that confronts the patient. The aim, then, is to modify the patient's reaction to the stress under which he labors, enable him to tolerate it with greater equanimity and restore him to full functional ability. Over the past several years many agents have appeared that alter emotional reactions by various activities within the central nervous system. Not all have proved satisfactory for use in office practice, since in many cases side effects, principally excessive sedation, preclude use of such substances for patients who live active lives. A new member of the 1,4-benzodiazepine series, of which chlordiazepoxide is also a derivative, came to my attention about four years ago. The pharmacological properties of the compound, oxazepam 0 (Fig. 1), as demonstrated in animals, are essentially the same as those of other members of the series, but there are fewer side reactions. Animal behavior studies! have °Serax,~ Wyeth

Laboratories.

September-October, 1965

demonstrated the ability of this compound to lessen intrapsychic tensions without the ataxic effects peculiar to the benzodiazepine nucleus. Various clinical trials 2 - 6 have corroborated the experimental observations. METHOD AND MATERIALS

The series treated in my office over a period of four years, which totaled 400 patients, is described in Table I. The great majority were young to middle-aged adults who were actively employed in industry or the home; only 23 (6%) were 65 years of age or older. Nine other patients had entered treatment but dropped out, usually after the first office visit. Anxiety was present in all; tension, depression, irritability and insomnia also were prominent presenting symptoms. Agitation, lethargy, autonomic and conversion reactions, obsessive thinking, compulsive behavior, and phobic and other reactions were observed in some patients. The severity of each emotional symptom diagnosed was exaluated at the initial visit.

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Fig. 347

PSYCHOSOMATICS TABLE I. 400 PATIENTS WITH ANXIETY AND DEPRESSION TREATED WITH OXAZEPAM IN A PRIVATE OFFICE PRACTICE 400 4 yean i to 83

Patients: Duration: Aile: A\'cra~e:

42 }'('ars

Males: Females: Duration of Therapy: A\'era~e:

Daily DOS3lle: Range A\'era~(":

Usual

startin~

._----

years

105 (26%) 295 (74'70) )·155 weeks 42 weeks

20

to

180

mI{. p~

day

60 mil. per day 40 to 60 mll. per day

Dose: -----------------

Two hundred fifty-six patients (64%) had received no previous treatment to relieve their emotional symptoms. Ataractic or sedative medication, with or without antidepressants, had been administered previously to 144 (36%). Sixty-four had received meprobamate in some form, 34 (9%) had received chlordiazepoxide, 20 had been treated with a phenothiazine derivativ~ or thioridazine, ~nd three had received barbiturate or nonbarblturate sedatives. Twenty-three had been treated with compounds specific for depression. One agent had been used for 94 patients (65 per cent of those who had been previously treated) 45 had required two in combination, four had needed three, and one had received four combined medications.

Dose. Oxazepam, in capsules of 10 or 15 mg., was prescribed in total daily doses of 20 to 180 mg. The starting dose was 40 to 60 mg. daily; the average, 60 mg. a day. (Table I.) Patients 16 to 65 years. ~f. age usually received 60 mg. per day Initially. Younger and older patients were started on 40 mg. per day. For 393 patients (98%) the total daily dose at no time exceeded 120 mg. Adjunctive medication. Three hundred thirty-four patients (84%), received no therapy but oxazepam. Fourteen received .meprobamate; six, a combination of promazIne and meprobamate; one, chlorpromazine; two, nonbarbiturate sedatives, and only three (0.007 per cent) required chlordiazepox~de. Forty who had exhibited pronounced eVIdences of depression received an antidepressant compound. In such cases the clinical res~onse to oxazepam in combination with an antidepressant is more favorable than to either agent alone. Some of these patients received the antidepressant for only a short time, after 348

which treatment with oxazepam alone sufficed. For 54, one adjunctive agent for control of emotional symptoms was required.

Duration of treatment ranged from five doses in one case and three days in another to 155 weeks (nearly three years), and averaged forty-two weeks. (Table I) Therapy for the entire series totaled 14,772 patient weeks. At the present time about 150 patients are still continuing to receive oxazepam in maintenance medication. Evaluation of response. To avoid contaminating the evaluation with the effects of any previously used medication or prolonged supportive therapy, the clinical result was graded four weeks after optimum response to treatment had been obtained. A numerical value (0,1,2,3) was assigned to the rated response of each emotional symptom, and the clinical effect of the medication on all symptoms was totaled and averaged to obtain the over-all clinical response. When 80 to 100 per cent relief of symptoms was achieved (rating of 3 reduced to 1 or 0, or severe modified to mild discomfort or complete disappearance of symptom), the effect was rated as excellent; 60 to 79 per cent improvement in all symptom categories (2 to 1, or moderate altered to mild discomfort) was graded as good; 40 to 60 per cent relief of all symptoms (3 to 2, or severe modified to moderate discomfort) was rated as fair; and little or no symptom improvement (0 to 39 no change) was rated as poor. Those whose symptoms were accentuated were graded as worse. Results. A satisfactory response (rating of excellent or good) was achieved in 84 per cent. In 11 per cent of patients the results were rated as fair, and in four per cent as poor. Three patients (less than 1%) became worse. After five doses to a few days of medication they were returned to treatment with chlordiazepoxide because of an untoward reaction to the medication. (Table II). Most TABLE II. CLINICAL RESPONSE OF 400 PATIENTS TO TREATMENT WITH OXAZEPAM

Excellent Good Fair Poor Worse

No. Patients

% of Patients

306 29 44

77.

18

i. II. 4.

400

100.

3

1.

Volume VI

THIRD SYMPOSIUM: ANXIETY AND DEPRESSION

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SYMPTOM ANXIETY

(~OOI

TENSION

139~)

~O

300

100

~oo

DEPRESSION LETHARGY

IRRITABILITY

1I0B)

INSOM IA

(120)

AGITATION

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Fig. 2. Appearance of symptoms and clinical response in 400 patients treated with Oxazepam.

satisfactory lessening of symptoms occurred in anxiety, tension, depression, insomnia, irritability, conversion and autonomic reactions, lethargy and agitation, in that order. (Fig. 2). In many cases depression seemed to lighten as the patient's anxiety and tension relaxed. Among the female patients, a syndrome that may be termed "cabin fever" was commonly seen. In the typical case the patient was usually between 30 and 40 years old, had been married ten years or more, had three or four children, and her husband was engrossed in his work and outside activities. The wife, meanwhile, was largely confined to the house, her interests were restricted to the children and she had little recreation. Her husband was too busy to give the attention, reassurance, and companionship she needed. As the wife became more and more unhappy and irritable with the children, anxiety, tension and conversion reactions, such as chest pain, developed. Finally she became depressed to such an extent that she was unable to function in the home, and was brought to the office for treatment. This type of patient responded favorably to oxazepam therapy. The initial effect of a single 15 or 30 mg. dose of oxazepam begins to be noticeable in twenty to thirty minutes; the full effect, within an hour and a half. The duration of emoSeptember-October, 1965

tional relaxation from a 15 mg. dose seems to be about four hours; from a 30 mg. dose, four to six hours. The treatment seemed to exert no significant influence on body weight. Two hundred sixty-six patients showed no change; 49 gained five and 19 gained ten pounds; 50 lost five and 16 lost ten pounds. Blood pressure was not affected except in those who had labile hypertension. In these the m€:dication provided a stabilizing effect. Liver function tests, urinalysis and complete blood counts were done at intervals of twenty weeks for 80 patients who continued under treatment on a long-term basis, that is, for two years or more. The findings in all cases were within normal limits. Sixteen patients, three of whom were more than 40 years old, became pregnant during treatment. Twelve delivered normal, healthy infants and four had miscarriages at six weeks. One of these again became pregnant and delivered a healthy infant at term.

Suicidal overdosage. In four years of evaluating the compound, two patients have attempted suicide. One, a 31-year-old, 92pound woman, ingested between 30 and 40 capsules of 15 mg. (450 to 600 mg.), and an unknown quantity of wine. The other, a 30year-old, 330-pound man, swallowed 50 cap349

PSYCHOSOMATICS

sules of 15 mg. (750 mg.). Both slept for twenty-four hours, without change in vital signs, and were somewhat lethargic for twenty-four hours after awakening, hut after forty-eight hours were completely normal. Blood levels were ohtained from the first patient, and showed a value of 0.6 mg. per 100 ml., which is considerahly more than would he expected from therapeutic doses. Liver function tests and hlood studies, done for the second patient, yielded findings within normal limits. The hlood level of oxazepam for this patient was 0.178 mg. per 100 ml., which is to he expected with therapeutic doses of 15 mg. four times a day. Side effects were evaluated as they occurred during treatment. (Tahle III.) ~fost patients experienced some drowsiness on start of therapy, hut this is sdf-limited and usually subsides after three or four doses. Reduction of the dose may he indicated in some cases. The transience of the sedative eflects was important in these patients since most of them work in industry and must be alert at all times. The rash experienced by one patient developed in three days; the stomatitis in another was rather severe. The paradoxical {'xcitahility is not unusual, and occurs commonly under medication with chlordiazepoxide, barbiturates, and also occasionally with promethazine in elderly and very young patients when the dose is inadequate. TABLE III. __

SIDE EFFECTS I:" 400 I'ATlE:"TS

TRE_~_T_ED~ WIlItOXA~EI''''~f

====

:'\0. patients

S.-dation. transient S.'cia t inn. persish"n I

Rash

Slomaliti~

Paradoxical (·xcitahilit,,·

25 I I I 3

SU:\I:\IARY

Four hundred patients, 74 per cent of whom were female, were treated in a private office practice for emotional symptoms, mainly anxiety, tension, irritability, insomnia and depression, that had originated in environmental, situational and disease-induced stress. Thirty-six per cent had been previously treated with various medications. Oxazepam was administered in total daily doses of 20 to 180 mg., with an average of 40 to 60 mg. daily. For 98 per cent the total 350

daily dose never exceeded 120 mg. One agent, oxazepam, sufficed for 84 per cent. Ten per cent required an antidepressant also, usually for a short time, after which oxazepam alone was sufficient. Duration of treatment ranged from a few days to nearly three years, with an average of six months, and totaled 14,772 patient weeks. A satisfactory result (rating of excellent or good response) was achieved in 84 per cent. Less than one per cent required chlordiazepoxide, whereas previously this agent had been used for nine per cent. Anxiety, tension, irritability, insomnia, autonomic reactions, lethargy, agitation and depression were the symptoms most satisfactorily relieved. Suicidal overdosage occurred in two patients; both recovered, without change in vital signs, within forty-eight hours. Side effects, usually transient drowsiness, which subsided after three or four doses, occurred in eight per cent. There was no significant influence on body weight or blood pressure; the findings of hlood studies, urinalysis and liver function tests done periodicallyon patients treated for two years or more were within normal limits. In this long-term clinical experience, oxazepam has proved a useful, safe, reliable, and flexihle therapeutic agent in the management of the office patient with anxiety tension states and anxiety reactions associated with depression.

ILLUSTRATIVE CASES

Case 1. J.H., a 68-year-old liquor store employee with a history of arteriosclerotic heart disease and one previous myocardial infarction became extremely anxious, tense and depressed, with inability to sleep, aher having been hospitalized for an episodt, of myocardial ischemia. Subsequently, the patient had frequent recurrent attacks of angina and with each attack hecame markedly anxious, depressed and fearful of death. The more anxious and tense he became tl1(' more frequent WNe the anginal attacks and his t'Onsumption of nitroglycerin rapidly increasP{1. Oxazepam was administered in daily doses of 60 mg., with pronounced reduction in anxiety; his dl'pressioll and insomnia disappeared. The anginal attacks became much less severe and frequent; the patient gainpd insight into his difficulties, and returned to work. Therapy has continued for thirty-five weeks; the patient is still und{'r medication. Case 2. A.C., a 56-year-old housewife experienced palpitation and chest pain and episodes of crying, and withdrew from many of her previous community activities. She had insomnia and anorexia. :\ brother in poor health, who lived with the patient, was hosVolume VI

THIRD SYMPOSIUM: ANXIETY AND DEPRESSION pitalized and a gastric carcinoma was diagnosed. The patient's anxiety, on this score, together with the neglect of her husband, whose work as a fire chief often kept him away from home at night, caused a severe exacerbation of her emotional symptoms. Oxazepam, 40 mg. daily, moderately reduced symptoms; increase of the dose to 60 mg. greatly lessened her anxiety, tension and depression. Insomnia and anorexia subsided. The patient has heen treated, up to the present for more than three years and is continuing.

Case 3. D.R., a 42-year-old housewife was seen because of intermittent epigastric distress, partially relieved by food, milk and antacids, which she had suffered for more than one year. Headache, palpitation and anterior chest pain also occurred. The epigastric pain was so severe that she was unable to carry out her household duties. She was placed on a strict ulcer regimen and oxazepam, 60 mg. daily. Anxiety, tension and chest pain were immediately and markedly reduced; palpitation and headache subsided completely. The diagnosis of duodenal ulcer was confirmed hy roentgenogram. After eight weeks of strict ulcer therapy, roentgeno-

graphic evidence of the ulcer disappeared. The patient no longer has epigastric pain, and is continuing the medication.

REFERENCES 1. Geller, I.: Relative potencies of benzodiazepines as measured by their effects on conflict behavior. Arch. Int. Pharmacodyn., 149:243-47, 1964. 2. Gerz, H. 0.: A preliminary report on the management of geriatric patients with oxazepam. Amer. ]. Psychint., 120: 1110, 1964. 3. Tobin, J. M., et aI.: Clinical evaluation of oxazepam for the management of anxiety. Dis. Nerv. Syst., 25:689-95, 1964. 4. Krakowski, A. J.: Suppression of anxiety with oxazepam in a private psychiatric practice. Psychosomatics, 6:26-31, Jan.-Feb. 1965. 5. Chesrow, E. J.: The use of oxazepam in the management of the geriatric patient with behavioral problems. Clin. Med., 72: 1001-05, June, 1965. 6. Gilbert, M. M.: Clinical trial of oxazepam for treatment of anxiety and tension in general practice. lnternat.]. Neuropsychiat. (In press).

590 East Chestnut Street Coatesville, Pennsylvania

Anti-Depressant Chemotherapy, 1965 Rapid Response to Serotonin Precursor Potentiated by Ritalin THEODORE R. ROBIE, M.D. and ALPHONSE FLORA, M.D. • Eight years ago, I confirmed Kline's findings that remission of melancholia could be induced by adequate dosage of iproniazid, without electro-convulsive therapy. Since then, tremendous progress has been made through psycho-chemistry in reducing disabling mental depression and reducing suicidal tendencies. \ Ve are still in the process of learning new methods to better protect our patients and must be prepared to treat chemotherapeutically induced hypotension. Also, we must face the possible reversal from depression to overproductivity and psychomotor over activity, which may occur in rare instances. These factors present the two-edged sward of overdosage. Marplan is a good drug to conside~' as an September-October, 1965

example. In most cases, dosage of 30 mg. daily will induce remission of depression in one to three weeks. If there is no improvement in seven to ten days, dosage should be increased to 40 mg. daily and may be increased to 50 mg. if the desired effects have not been realized in the next ten days. In raising the dose, one must be guided by the severity of hypotension, if present, especially in patients unable to make frequent office visits. The bulk of my patients are ambulatory, many coming from a distance, so I decided to venture teaching the patient or relative to record blood pressures at home. The Taylor Instrument Company loaned me sphygmomanometers and stethoscopes for this purpose. To prescribe anti-depressants without 351