Study Title and Description
Caffeine challenge test in panic disorder and depression with panic attacks.
Key Questions Addressed
|1||For [population], is caffeine intake above [exposure dose], compared to intakes [exposure dose] or less, associated with adverse effects on behavior*?|
Primary Publication Information
|Title||Caffeine challenge test in panic disorder and depression with panic attacks.|
|Author||AE Nardi,FL Lopes,AM Valença,RC Freire,AB Veras,VL de-Melo-Neto,I Nascimento,AL King,MA Mezzasalma,GL Soares-Filho,WA Zin,|
Secondary Publication Information
There are currently no secondary publications defined for this study.
Extraction Form: Behavior - Design Details - INCLUDED Studies
No arms have been defined in this extraction form.
|Question... Follow Up||Answer||Follow-up Answer|
|What outcome is being evaluated in this paper?||Behavior|
|What is the objective of the study (as reported by the authors)?||Our aim was to observe if patients with PD and patients with major depression with panic attacks (MDP) (Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition [DSM-IV] criteria) respond in a similar way to the induction of panic attacks by a caffeine challenge test. We also decided to try to discriminate patients with panic attack (PD and MDP) from patients with MD, as these groups might have some differences—physiological or psychopathologic—in relation to the anxiety response level to the caffeine challenge test.|
|Provide a general description of the methods as reported by the authors. Information should be extracted based on relevance to the SR (i.e., caffeine related methods)||We selected the patients for this trial from a sample of PD and MD patients in their first visit to our center. During the period of selection, all first-visit patients (n = 143) were examined to determine if they fulfilled the inclusion criteria. If so, they were invited to participate in our trial. All patients were medication-free upon presentation to our center. They had their disorder for more than 3 months but less than a year. They had no caffeine abuse and their mean usual intake of caffeine products was about 100 mg a day. This 24-hour intake did not induce any withdrawal symptoms for the prestudy 1-week caffeine-free period. A group of 28 subjects with no family history of anxiety or mood disorder (20 women and 8 men; mean age F SD, 35.2 F 8.8 years) was used for comparison. After having received a clinical diagnosis of PD, MD, or MDP made by a study psychiatrist, the subjects were interviewed by a second clinician with the Structured Clinical Interview Diagnostic (SCID)  for DSM-IV . The protocol was explained to the subjects, who signed a voluntary written consent form to participate in the study. The subjects were informed that they would be asked to drink different coffee solutions and that the procedure was not dangerous but that anxiety symptoms could occur during the session. Our local ethics committee approved the protocol, which complied with the principles of the Declaration of Helsinki. The inclusion criteria were age 18 to 55 years, occurrence of at least 3 panic attacks in the 2 weeks before the first challenge test day in PD and MDP patients, no use of any psychotropic drugs for at least 4 weeks by any subject, and a urine test negative for benzodiazepines and other medications before the test. Exclusion criteria were unstable medical condition, cognitive-behavior psychotherapy during the study, use of any regular antipsychotic, antidepressant, regular benzodiazepine or nonbenzodiazepine anxiolytic medication for 4 weeks, or fluoxetine for 5 weeks before the test, or the presence of suicidal risk. Smokers and subjects with a history of respiratory disease were excluded. The comparison group was also assessed by the SCID . They were free of any history of or current panic disorder, major mood disorder, schizophrenia, and current substance use disorders. They also had no family history of moderate to severe anxiety or mood disorders. All subjects underwent a physical and laboratory examination to ensure they were healthy enough to participate in the challenge test. They had no respiratory or cardiovascular abnormalities and were free of caffeine ingestion for 1 week. The test was conducted in the usual examination room, with no changes made in the environment. To measure the baseline anxiety level, before drinking the coffee, subjects were asked to complete the Subjective Units of Disturbance Scale (SUDS), a semiquantitative evaluation method with scores ranging from 0 (no anxiety) to 10 (maximum anxiety) , and the Diagnostic Symptom Questionnaire (DSQ)  adapted for DSM-IV in which the presence and level of discomfort of panic symptoms experienced after drinking the coffee solutions were rated on a 0 to 4 point scale (0 = none, 4 = very severe). Both self-rating scales, the SUDS and the DSQ, had been tested by back translation. The SUDS and DSQ were completed again 30 minutes after the coffee solution intake. The subjects completed them independently of the raters. On the basis of the DSQ, a panic attack was defined by objective raters as the following: (1) 4 or more symptoms of a panic attack from the DSM-IV (palpitations, sweating, trembling, smothering, feelings of choking, chest pain, abdominal distress, dizziness, derealization); (2) at least one of the cognitive symptoms of a panic attack from the DSM-IV (eg, fear of dying or of losing one’s sanity or control); (3) feeling of panic or fear, similar to spontaneous panic attacks, recorded on a card that the raters were not permitted to observe; and (4) agreement at clinical diagnosis evaluation between 2 diagnosis-blinded raters from the team during the test. We explained to the subjects what they were expected to do and they relaxed for an additional 10 minutes, after which we gave them the coffee solution. In a randomized double-blind experiment performed in 2 occasions 7 days apart, an oral dose of 480 mg of caffeine or a caffeine-free (placebo) solution were administered in the form of instant coffee, produced regularly by a commercial coffee company. The decaffeinated coffee contained a small amount of caffeine, as more than 97% of the caffeine is removed, resulting in less than 5 mg of caffeine intake. The source of caffeine used does not guarantee that the doses given in the challenges were exact. Most caffeine products (eg. caffeine citrate) are quite bitter. To deal with the caffeine-free drink (placebo) we used 2 tablets of a low-energy sweetener, sucralose (0.84 joules per tablet), in the caffeine and in the caffeine-free drinks. The patient was requested to drink the coffee solution within a period of 15 minutes, after which a 30-minute period followed to allow the caffeine to reach its peak levels in the blood . 2.1. Statistical analysis Panic rates for the 4 groups, also separated according to rater and subject ratings and by gender, were compared by the v2 test. Data concerning the effects of caffeine and time of observation were tested by 2-way analysis of variance (ANOVA) with repeated measures for time and independent groups for SUDS (before and after) and heart rate (before, 15 minutes and 30 minutes after). Pairwise comparisons of the treatment groups were performed at end point using Fisher protected least significant difference method. For identifying heart rate difference among groups, a 1-way ANOVA was used for time difference using Fisher protected least significant difference method. The level of significance was set at 5%.|
|How many outcome-specific endpoints are evaluated?||1|
|What is the (or one of the) endpoint(s) evaluated? (Each endpoint listed separately)||anxiety|
|List additional health endpoints (separately).|
|List additional health endpoints (separately)|
|Notes||occurrence of panic attack was also measured, though the control group was not explicitly compared to any other for this measure|
|What is the study design?||Controlled Trial|
|Randomized or Non-Randomized?||NCT|
|What were the diagnostics or methods used to measure the outcome?||Subjective|
|Optional: Name of Method or short description||Subjective Units of Disturbance Scale (SUDS), a semiquantitative evaluation method with scores ranging from 0 (no anxiety) to 10 (maximum anxiety) , and the Diagnostic Symptom Questionnaire (DSQ)  adapted for DSM-IV in which the presence and level of discomfort of panic symptoms experienced after drinking the coffee solutions were rated on a 0 to 4 point scale (0 = none, 4 = very severe).|
|What was the reference, comparison, or control group(s)? (e.g. high vs low consumption, number of cups, etc.)||decaffeinated coffee (< 5mg) compared to coffee containing approximately 480 mg|
|What were the listed confounders or modifying factors as stated by the authors? (e.g. multi-variable components of models. Copy from methods)||N/A|
|Provide a general description of results (as reported by the authors).||All subjects showed an increase in anxiety levels after drinking the caffeine solution. Significantly more PD and MDP patients had a panic attack in response to the 480-mg caffeine intake than MD patients or the control group according to both rater groups: 58.6% (n = 17) of patients with PD, 44.4% (n = 12) of patients with MDP, 12.0% (n = 3) of patients with MD, and 7.1% (n = 2) of control subjects had a panic attack after the caffeine challenge test (chi-squared = 16.22, P = .001). No patient had a panic attack after the caffeine-free solution. The MD patients and the healthy control group had a nonsignificant increase in anxiety levels (MD vs control, P = .266).|
|Did the authors perform a dose-response analysis (or trend/related analysis)?||No|
|What were the authors's observations re: trend analysis?|
|What were the author's conclusions?||Our results indicate that those subjects who have anxiety problems are more likely to panic in response to the caffeine challenge test. In our sample, the 480-mg caffeine challenge test differentiated PD and MDP patients from MD patients and healthy controls.|
|What were the sources of funding?||Supported by the Brazilian Council for Scientific and Technological Development grant 554411/2005-9.|
|What conflicts of interest were reported?||N/A|
|Does the exposure (dose) need to be standardized to the SR?||No|
|Provide calculations/conversions for the exposure based on the decision tree in the guide (for all endpoints/exposure levels of interest).|
|List all the endpoint(s) followed by the dose (mg) which will be used in comparison to Nawrot. Characterize value as LOAEL/NOAEL, etc. if possible.||Anxiety - NOAEL = 480 mg/day|
|Notes regarding selection/listing of endpoints and exposures/doses to be compared to Nawrot.||single dose no effect at levels higher than Nawrot. Authors note that the dose given may be exact since it was estimated from brewed coffee. 2/28 healthy controls experienced a panic attack where as no one experienced a panic attack with placebo.|
|What is the importance of the study with respect to the adverseness of the outcome?||Important|
No baseline characteristics have been defined for this extraction form.
Results & Comparisons
No Results found.
|Arm or Total||Title||Description||Comments|
No quality dimensions were specified.
No quality rating data was found.