Idiopathic Intracranial Hypertension Is Associated with Depression Regardless of Weight: A Controlled Study ()
1. Introduction
Idiopathic intracranial hypertension (IIH), known also as pseudotumor cerebri, is quite a not rare disease [1]. It affects mainly young obese women during their childbearing years [2]. Its incidence in this group is estimated to be 20 per 100,000 per year [3]. It is characterized mainly by headache, visual loss and pulsatile tinnitus [4]. This entity could be associated with severe disability, and its negative impact on the quality of life of these patients could be tremendous, including depression [5].
Few studies only were performed addressing the issue of depression in IIH [5] [6]. In one study, depression among IIH patients was attributed partially to obesity. In another study, IIH was associated with depression more than in the general population, but comparable to women with migraine.
On the other hand, some studies also showed a causative correlation between obesity and depression [7] [8]. This causative correlation between obesity and depression was attributed to low levels of glutamine among obese patients. So, it is not clear whether weight by itself has a significant role in the development of depression among these patients.
HAM-D is a reliable questionnaire that is widely used in clinical trials to assess patients who might have a depressive disorder [9]. It is a reliable and reproducible questionnaire.
In this study, we prospectively evaluated patients with IIH and an age- and weight-matched group from the same population, for the existence of depression, using the HAM-D questionnaire.
2. Materials and Methods
Non-selected controlled IIH patients who came to follow-up examination were sequentially prospectively recruited from the neuro-ophthalmology clinic at Tzafon Medical Center, Poria. Following consent, patients were frontally interviewed by the same investigator and completed the HAM-D questionnaire with them.
As mentioned earlier, HAM-D is a reliable questionnaire that has been widely used in clinical trials for many years to assess patients who might have a depressive disorder [9] (Appendix). It covers items such as mood, feelings of guilt and suicide, insight, anxiety, agitation, insomnia, work activities, somatic symptoms, genital symptoms, hypochondriasis, weight and others. The score range from zero up to four in some items and from 0 to 2 in others. It is reliable and reproducible with a consistency rate of 0.8, and inter-examiner reliability of 0.8 - 0.98. The test-pre-test reliability and validity are 0.65 and 0.91 compared to severity of depressive borderline criteria. In this questionnaire, scores between 0 - 9 rules out depression, 10 - 13 represent mild depression, 14 - 17 represent moderate depression, Scores > 17 indicates severe depression, and 23 or more represent a very severe depression.
Inclusion criteria included diagnosis of IIH according to modified Dandie’s Criteria, women only, age between 18 and 48 years, follow-up duration of at least 6 months at our neuro-ophthalmology clinic, patients with improved symptoms and signs under treatment. Exclusion criteria included failure of medical treatment in terms of improvement of papilledema and headaches frequency, and patients with a known diagnosis of psychiatric disorder including depression.
An age and weight-matched group from the same population (each patient was asked to bring with him a friend with about the same weight and age, but not a relative) was asked to participate as control group, and interviewed the same way as the patient’s group, after consent. This way of control group recruitment is in order to minimize biases related to social background among the patients’ and control groups, which could have impact on tendency towards depression. Both groups were interviewed by the same investigator (LN) who was blinded to the existence of IIH among the participants.
For statistical analysis, Chi-square test was used between the categorical parameters of the demographics, and unpaired t-test was used to compare between the scores of each item of the questionnaire, of both patients and controls.
This study was approved by the local ethics committee of the Tzafon Medical Center.
The approval # was 0092-19-POR, and the study was conducted and performed according to the Declaration of Helsinki.
3. Results
Table 1 summarizes the demographics of the patients. No significant difference was observed between the different parameters of both groups. Most of the participants of both groups (patients and control) were young (28.6 years vs 32.47, respectively) and obese (BMI of 32.8 vs 32.1 respectively).
Table 1. Demographic of both patients’ and control groups.
| Parameter |
Result |
P value |
| Patients |
Control |
| -Age |
28.6 ± 7.51, 18 - 45 |
32.47 ± 8.22, 18 - 48 |
0.07 |
| -Single: Married |
10:22 |
12:16 |
0.369 |
| -Academic education |
17:15 |
16:12 |
0.443 |
| -Employed |
22:10 |
19:9 |
0.942 |
| -BMI |
32.8 ± 6.87, 19.3 - 43 |
32.1 ± 3.78, 28.4 - 42.5 |
0.621 |
Table 2. Questionnaire result among patients, and control groups.
| Parameter |
ResultPatient group |
ResultControl group |
P value |
| -Depressed mood |
1.41 ± 1.10, 0 - 4 |
0.571 ± 0.991, 0 - 4 |
0.003 |
| -Feelings of guilt |
0.594 ± 0.875, 0 - 3 |
0.107 ± 0.315, 0 - 1 |
0.005 |
| -Suicide |
0.344 ± 0.902, 0 - 4 |
0.036 ± 0.189, 0 - 1 |
0.082 |
| -Insomnia-initial |
1 ± 0.842, 0 - 2 |
0.071 ± 0.262, 0 - 1 |
0.000 |
| -Insomnia-delayed |
0.656 ± 0.787, 0 - 2 |
0.357 ± 0.559, 0 - 2 |
0.092 |
| -Insomnia-middle |
0.5 ± 0.622, 0 - 2 |
0.179 ± 0.476, 0 - 2 |
0.028 |
| -Work and activities |
0.937 ± 1.162, 0 - 3 |
0.036 ± 0.189, 0 - 1 |
0.000 |
| -Retardation |
0.406 ± 0.712, 0 - 3 |
0.071 ± 0.262, 0 - 1 |
0.018 |
| -Agitation |
0.719 ± 0.813, 0 - 2 |
0.429 ± 0.573, 0 - 2 |
0.113 |
| -Anxiety-psychic |
1 ± 0.916, 0 - 2 |
0.607 ± 0.629, 0 - 2 |
0.055 |
| -Anxiety-somatic |
0.906 ± 1.088, 0 - 3 |
0.179 ± 0.476, 0 - 2 |
0.001 |
| -Somatic symptoms* |
0.656 ± 0.787, 0 - 2 |
0.036 ± 0.189, 0 - 1 |
0.000 |
| -Somatic symptoms general |
0.844 ± 0.847, 0 - 2 |
0.036 ± 0.189, 0 - 1 |
0.000 |
| -Genital symptoms |
0.344 ± 0.543, 0 - 1 |
0.000 ± 0.000, 0 - 0 |
0.001 |
| -Hypochondriasis |
0.469 ± 0.803, 0 - 2 |
0.464 ± 0.744, 0 - 2 |
0.002 |
| -Weight loss |
0.308 ± 0.480, 0 - 1 |
0.000 ± 0.000, 0 - 0 |
0.001 |
| -Insight |
0.531 ± 0.507, 0 - 1 |
0.000 ± 0.000, 0 - 0 |
0.001 |
| Total score |
11.62 |
3.179 |
0.000 |
*Somatic symptoms-Gastrointestinal.
Table 2 summarizes the scores of the different items of the questionnaire results. There was a significant difference between the patients and control group in nearly all the parameters with a mean score of 11.62 (indicative of depression) vs 3.179 (normal) (P = 0.000), indicating mild depression among the patients’ group.
The most significant differences between the patients, and control groups included items of insomnia initial, work and activities and somatic symptoms. Three items only had no significant difference, though were on the edge of significance, and included suicide, insomnia delayed and psychic anxiety.
4. Discussion
The most important finding in our study is that IIH is strongly associated with depression, though mild, and that this correlation is irrelevant to the BMI of the patients. The significance of findings was observed in nearly all the items of the questionnaire with huge gap between the mean score among the patients’ group (11.62) compared to the control group (3.179, P = 0.000). The control group of obese persons had no indication of depression.
These results should encourage the neuro-ophthalmologist to refer patients diagnosed with IIH for the evaluation of depression. Generally, there is no known contraindication of anti-depressants with the treatment of IIH.
The items of the questionnaire with the most significant scores were insomnia-initial, work + activities and somatic symptoms. Quality of sleep is an important factor for quality of life [10]. Insomnia by itself is significantly associated with depression [11]. Unemployment is also known as a strong risk factor for the development of depression [12]. It is also known that there is a strong correlation between inactivity and depression, and that small doses of physical activity can lower risks of depression [13]. Somatic symptoms are known predictors for the identification of subthreshold depression up to major depressive disorders in primary care settings [14].
It is interesting to note that among three items of the questionnaire; suicide, insomnia-delayed and anxiety, the scores were on the edge of significance, while there was no difference with the item of agitation. So, it seems with existing various symptoms of depression of the questionnaire among our patients, the risk of suicide in some way is diminished, reducing the fear in some way of this dreadful complication.
Agitation by itself, could also be observed in different situations, other than depression [15]. There are no studies also showing a protective effect of obesity against agitation.
The mechanism of depression in IIH is most probably related mainly to the disability of these patients from the symptoms of IIH, mainly headache, visual loss, pulsatile tinnitus and maybe due to other factors.
Several studies had shown that headache is a risk factor for the development of depression [16] [17]. These studies included patients with headaches due to different reasons, such as migraine. There are no studies in the literature about the association between visual loss and/or tinnitus with depression. Studies evaluating the correlation between visual loss or pulsatile tinnitus with depression are needed.
It must be remembered that our study included only patients with controlled IIH patients. Patients without treatment or with recent diagnosis, most probably would have higher scores of the questionnaire.
The question remains if other mechanisms play a role in the development of depression, or depression itself is a risk factor for the development of IIH. All of our patients reported that the changes in mood they experience, started following headache (data not shown). We also are not aware of studies linking acetazolamide treatment of IIH, with depression. We did not find studies in the literature comparing the scores of HAM-D questionnaire at presentation or early stages of the disease compared to the period under control.
The drawbacks of our study is the small number of our patients. However, the scores of our study were relatively consistent. Future prospective studies with larger number of patients are needed. Sometimes, interviewer-assisted questionnaires could be associated with some biases [18]. In our study, the interviewer tried as much as he could to give the same information and assistance, equally between the different patients, in addition to being blinded to the existence of IIH among the participants.
In summary, our results added new information about the association between IIH, obesity and depression, and more studies with large number of patients are needed in the future.
5. Conclusion
IIH patients had significantly higher HAM-D scores irrelevant to the weight of the patient. Psychological support in addition to the conventional treatment of IIH, is needed to improve the quality of life of these patients.
Data Availability
Data is available upon request.
Appendix: Hamilton Depression Rating Scale
|
Pre-treatment |
1st Follow-up |
2nd follow-up |
| HAM-D Ratting Scale Symptoms |
Date |
Date |
Date |
| 1 Depressed mood |
0 1 2 3 4 |
0 1 2 3 4 |
0 1 2 3 4 |
| 2 Guilt feelings |
0 1 2 3 4 |
0 1 2 3 4 |
0 1 2 3 4 |
| 3 Suicide |
0 1 2 3 4 |
0 1 2 3 4 |
0 1 2 3 4 |
| 4 Insomnia-early |
0 1 2 |
0 1 2 |
0 1 2 |
| 5 Insomnia-middle |
0 1 2 |
0 1 2 |
0 1 2 |
| 6 Insomnia-late |
0 1 2 |
0 1 2 |
0 1 2 |
| 7 Work and activities |
0 1 2 3 4 |
0 1 2 3 4 |
0 1 2 3 4 |
| 8 Retardation and psychomotor |
0 1 2 3 4 |
0 1 2 3 4 |
0 1 2 3 4 |
| 9 Agitation |
0 1 2 3 4 |
0 1 2 3 4 |
0 1 2 3 4 |
| 10 Anxiety-psychological |
0 1 2 3 4 |
0 1 2 3 4 |
0 1 2 3 4 |
| 11 Anxiety-somatic |
0 1 2 3 4 |
0 1 2 3 4 |
0 1 2 3 4 |
| 12 Somatic symptoms GI |
0 1 2 3 4 |
0 1 2 3 4 |
0 1 2 3 4 |
| 13 Somatic symptoms-General |
0 1 2 |
0 1 2 |
0 1 2 |
| 14 Sexual dysfunction-Menstural disturbance |
01 2 |
01 2 |
01 2 |
| 15 Hypochondriasis |
0 1 2 3 4 |
0 1 2 3 4 |
0 1 2 3 4 |
| 16 Wight loss by history |
0 1 2 |
0 1 2 |
0 1 2 |
| By scale |
0 1 2 |
0 1 2 |
0 1 2 |
| 17 Insight |
0 1 2 |
0 1 2 |
0 1 2 |
Assessment is recommended at two weekly intervals.
HAM-D score level of depression: 10 - 13 mild; 14 - 17 mild to moderate; > 17 moderate to severe.