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Choice of antidepressants: questionnaire survey of psychiatrists and general practitioners in two areas of Sweden

^a Department of Clinical Neuroscience and Family Medicine, Section of Psychiatry, Karolinska Institute, Huddinge University Hospital, S-141 86 Huddinge, Sweden, ^b Centre for Suicide Research and Prevention, Karolinska Hospital, Stockholm, Sweden, ^c Department of Medical Laboratory Sciences and Technology, Division of Clinical Pharmacology, Karolinska Institute, Huddinge University Hospital, Huddinge,

Correspondence to: Dr Isacsson.

Abstract

Objective: To identify factors that affect physicians' choice of specific antidepressant drugs in order to evaluate the validity of epidemiological studies of the risks (particularly suicide) and benefits of different compounds.
Design: Questionnaire survey of 264 psychiatrists and general practitioners in an urban area and a rural area of Sweden with validation of data by independent prescription surveys.
Setting: Urban area of greater Stockholm and rural county of Jamtland, Sweden. Subjects--228 physicians (86%) who answered the questionnaire.
Main outcome measures: The drugs used as first line drugs of choice, as drugs of choice in particularly severe depression, and as drugs of choice for disorders other than depression.
Results: Amitriptyline was the most common first line drug of choice among both psychiatrists and general practitioners. The patterns of choice of antidepressants in the two areas accorded with prescribing patterns in two independent prescription surveys. Amitriptyline was chosen even more frequently for severe depression and depression with severe insomnia. Clomipramine was chosen comparatively more often for depression with severe anxiety. Low toxicity compounds (mainly lofepramine, mianserin, and moclobemide) were more often the drug of choice in depression associated with overt risk of suicide. Amitriptyline and clomipramine were used extensively for disorders other than depression (40% and 54% of prescriptions, compared with 13-19% for some other major antidepressants).
Conclusion: Patient groups treated with different antidepressant compounds may not be comparable with respect to diagnoses and severity of disease. In particular, lofepramine, mianserin, and moclobemide, and possibly amitriptyline, seem to be chosen more often for patients prone to suicide.

TABLE V--Prescriptions per diagnostic category. Data are from diagnosis and prescription survey 1990-2. Prescription numbers are
extrapolated from sample of prescribers. Drugs with fewer than 100 observations excluded
--------------------------------------------------------------------------------------------------------------------------------
                               Clomipramine    Lofepramine    Amitriptyline   Maprotiline     Mianserin      Moclobemide
                               ------------    -----------    -------------   -----------   ------------   ---------------------
                                 No       %     No       %     No        %     No       %     No       %     No       %
--------------------------------------------------------------------------------------------------------------------------------
Depression                     164 486   46   86 448    87   188 381    60   68 524    82   69 743    86   58 390    81
Anxiety disorder               123 975   35      471    >1    18 634     6    1 799     2    7 008     9    5 681     8
Obsessive-compulsive disorder   13 689    4        0     0     1 184    >1        0     0        0     0      506     1
Pain                            15 781    4    2 207     2    38 258    12    1 266     2      800     1      581     1
Other psychiatric symptoms      23 383    7    4 160     4    52 651    17    6 879     8    2 345     3    3 203     4
Other somatic symptoms          17 168    5    6 301     6    17 078     5    4 614     6    1 020     1    4 019     6
--------------------------------------------------------------------------------------------------------------------------------
Total                          358 482  100   99 587   100   316 186   100   83 082   100   80 916   100   72 380   100

Discussion
In risk-benefit comparisons of antidepressant compounds it is essential to know whether the compounds are prescribed to comparable patient groups. This issue was approached by questioning the prescribers about their treatment rationale. The study group comprised over 3% of all Swedish doctors in psychiatry and general practice. Taken from one urban area with a medical school and from one rural area, the sample was likely to provide an accurate picture of the prescribing habits of Swedish psychiatrists and general practitioners.
The high correlation between the responses from the two study areas (table I) suggests that the sample was representative. The high response rate (86%) indicates that the survey was judged not to be controversial or intrusive by the physicians approached and that the topic was important. The high correlation between the responses regarding the first line choice of antidepressant and the actual prescribing practice, as found in independently conducted prescription surveys in the two areas, strongly supports the validity of our findings (table I). Further support comes from comparison of the responses regarding prescribing for other indications with those reported in the diagnosis and therapy survey (tables IV and V), from the intergroup consistency of responses (table I), and from the face validity of the findings (tables II and III).
Forty respondents either preferred not to or could not answer the question regarding their first line drugs of choice. Probably they did not have a first line drug of choice but chose drugs according to patients' symptoms (table III). This subgroup was at least as experienced as the whole study group. Some commented that they had two "first line drugs," one sedating and one non-sedating, and 36 (90%) answered at least one of the subsequent questions regarding particular types of depression. This reflects the difficulties in devising an uncomplicated questionnaire to investigate a complex problem.
Particularly severe depression and depression characterised by severe insomnia or by an overt risk of suicide may be associated with a higher risk of suicide. Most respondents (49-78%) did not switch from their first line choice in these types of depression (table II). However, a minority indicated that they switched to amitriptyline for severe depression, to the sedating compounds amitriptyline, trimipramine, and maprotiline for severe insomnia, and to the compounds with lower toxicity in overdose (lofepramine, mianserin, and moclobemide) in cases of overt risk of suicide (table III). This suggests that more severely ill patients are treated with these drugs. In particular, more suicidal patients may be treated with lofepramine, mianserin, and moclobemide. This may explain why moclobemide and mianserin were associated with an excess risk of suicide compared with amitriptyline in a Swedish toxicological study of 3400 suicides. Clomipramine was chosen more often for depression with severe anxiety, which may increase the association of clomipramine with suicide, as comorbidity between major depressive disorder and anxiety disorder has been reported.
Almost all prescribers had prescribed antidepressants for disorders and symptoms other than depression. Clomipramine or amitriptyline was used almost exclusively (table IV). Half of the clomipramine prescriptions and a third of the amitriptyline prescriptions were for diagnoses other than depression according to the diagnosis and therapy survey (table V). This pattern of use might give a weaker association with suicide for these drugs compared with those used exclusively for depression.
That lofepramine was the first line choice five times more often among general practitioners than among psychiatrists (table I) might possibly weaken the association of lofepramine with suicide. But this would be true only if depressed patients consulting general practitioners were at lower risk of suicide than those consulting psychiatrists. In a study in Jamtland more patients committing suicide were being treated by general practitioners than by psychiatrists.
CONCLUSION
Clomipramine and amitriptyline seem to find substantial use in patients other than those with depression, possibly tending to weaken the association of these drugs with suicide. On the other hand, the use of amitriptyline was also comparatively greater in depression with features associated with increased risk of suicide (severity, insomnia). The less toxic substances lofepramine, mianserin, and moclobemide seem to be in proportionally greater use in overtly suicidal patients, which may strengthen their association with suicide. These factors should be taken into account when comparing the associations of different antidepressants with suicide in epidemiological studies, as they may confound the impact of pharmacological properties of the drugs.

We thank general practitioners Kjell Nyman and Birgitta Danielsson for supporting the survey, Professor Gunnar Eklund for statistical advice, and Pia Inoue for assistance. The National Corporation of Pharmacies, Sweden, provided data from the diagnosis and therapy survey. The study was supported by grants from the Karolinska Institute and the Bank of Sweden Tercentenary Foundation.

Appendix

Questionnaire items

(1) How many patients do you treat at present with antidepressants?
Alternative answers: 0, 1 or 2, 3 or 4, 5-10, > 10.

(2) How many patients do you estimate that you have ever treated with
antidepressants? Alternative answers: 0, 1-9, 10-19, 20-100, >100.

(3) Which antidepressant do you prescribe as first line (one
alternative)? Alternative answers: Saroten (amitriptyline), Tryptizol
(amitriptyline), Tofranil (imipramine), Ensidon (opipramol), Tolvon
(mianserin), Tymelyt (lofepramine), Concordin (protriptyline), Fevarin
(fluvoxamine), Anafranil (clomipramine), Noritren (nortriptyline),
Sensaval (nortriptyline), Surmontil (trimipramine), Aurorix
(moclobemide), Pertofrin (desipramine), Ludiomil (maprotiline), "not
applicable."

(4) Is there any one of these drugs that you mainly prescribe if you
consider the depression to be particularly severe? Alternative answers:
see question 3.

(5) Is there any one of these drugs that you mainly prescribe if the
depression is associated with particularly severe insomnia? Alternative
answers: see question 3.

(6) Is there any one of these drugs that you mainly prescribe if the
depression is associated with a particularly severe anxiety state?
Alternative answers: see question 3.

(7) Is there any one of these drugs that you mainly prescribe if you
think there is a risk of suicide? Alternative answers: see question 3.

(8) Have you ever prescribed antidepressants for indications other than
depression? If "yes" state which other indications (for example,
obsessive-compulsive disorder, panic disorder, pain), which drugs you
have chosen, and roughly how many patients you have treated in this way.
[A table is provided for answers in which the drug used and the number
of patients should be stated for each indication.]

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