Случай злоупотребления кока-колой в рамках депрессии

BACKGROUND: Cola is an extremely popular caffeinated soft drink. The media have recently cited a poll in which 16% of the respondents considered themselves to be addicted to cola soft drinks. We find the contrast between the apparent prevalence of cola addiction and the lack of scientific literature on the subject remarkable. To our knowledge, this is the first case of cola dependency described in the scientific literature.
CASE PRESENTATION:
The patient is a 40-year-old woman, who when feeling down used cola to give her an energy boost and feel better about herself. During the past seven years her symptoms increased, and she was prescribed antidepressant medication by her family doctor. Due to worsening of symptoms she was hospitalised and later referred to a specialised outpatient clinic for affective disorders. At entry to the clinic she suffered from constant tiredness, lack of energy, failing concentration, problems falling asleep as well as interrupted sleep. She drank about three litres of cola daily, and she had developed a metabolic syndrome.The patient fulfilled the ICD-10 criteria for dependency, and on the Yale Food Addiction Scale (YFAS) she scored 40 points. Her clinical mental status was at baseline assessed by the Major Depression Inventory (MDI) = 41, Hamilton Depression - 17 item Scale (HAMD-17) = 14, Young Mania Rating Scale (YMRS) = 2 and the Global Assessment of Functioning (GAF) Scale = 45.During cognitive therapy sessions she was guided to stop drinking cola and was able to moderate her use to an average daily consumption of 200 ml of cola Her concentration improved and she felt mentally and physically better. At discharge one year after entry her YFAS was zero. She was mentally stable (MDI =1, HAMD-17 = 0, YMRS = 0 and GAF = 85) and without antidepressant medication. She had lost 7.2 kg, her waistline was reduced by 13 cm and the metabolic syndrome disappeared.
CONCLUSION:
This case serves as an example of how the overconsumption of a caffeinated soft drink likely was causing or accentuating the patient's symptoms of mental disorder. When diagnosing and treating depression, health professionals should pay attention to potential overuse of cola or other caffeinated beverages.

 A case of cola dependency in a woman with recurrent depression.

Психические расстройства при злоупотреблении кофеином

Causes

* The means by which caffeine exerts its pharmacologic effects remains a subject of active research.
* A leading theory suggests that caffeine is an adenosine receptor antagonist that blocks 2 major types of adenosine receptors, A1AR and A2AAR.9
* Adenosine is an inhibitory neuromodulator affecting norepinephrine, dopamine, and serotonin activity.
* Caffeine's putative antagonism of adenosine would increase those neurotransmitters promoting psychostimulation.
* The same neurotransmitter systems are implicated in the pathophysiology of several psychiatric disorders.

Caffeine-Related Psychiatric Disorders

This higher ratio means that smokers need three to four times the caffeine "dosage" as nonsmokers on average to get the same plasma caffeine levels...
Thus smoking or caffeine intake should not influence the dosing of risperidone and aripiprazole (metabolized by CYP2D6 and CYP3A), quetiapine (mainly metabolized by CYP3A), and ziprasidone (mainly metabolized by an aldehyde oxidase and CYP3A). On the other hand, the metabolism of clozapine and olanzapine is mainly dependent on CYP1A2 and UGTs. Table 1 summarizes studies that describe smoking's effects on the dosing of clozapine and olanzapine. Because caffeine has the opposite effect of smoking and increases the levels of clozapine and olanzapine, studies of caffeine interactions are also reviewed in the table. The effects of caffeine on CYP1A2 are explained by competitive inhibition. The effects of inhibitors are seen sooner than those of inducers, which require CYP1A2 synthesis...
The width of the therapeutic window determines the clinical significance of the plasma level changes associated with smoking and caffeine intake. Compared with olanzapine, clozapine has a much narrower therapeutic window...
Table 1 provides an average smoking correction factor of 1.5 for clozapine. If a patient who is taking clozapine smokes, smoking cessation would probably cause an average patient's plasma clozapine level to increase by 1.5 two to four weeks later. Similarly, if a patient who is stabilized in a nonsmoking environment starts to smoke more than one pack a day, the clinician may need to consider increasing the clozapine dose by a factor of 1.5 over two to four weeks. Checking for side effects and measuring the clozapine level may then be prudent, because the 1.5 factor is a gross approximation.

Gender may also influence clozapine metabolism. The limited information available (3,4) suggests that an average female nonsmoker requires low clozapine dosages (around 300 mg per day) to reach therapeutic levels, whereas an average male heavy smoker requires high dosages (around 600 mg per day). The required dosages for male nonsmokers and female smokers fall in between these numbers. Obviously, these are average results and may not apply to specific individuals. In the future, it is hoped that a better understanding of genetics may help to individualize clozapine doses. A CYP1A2 genetic variation may influence how patients respond to smoking's inductive effects. However, in a recent study this variation did not have any effects on clozapine levels in the clinical environment (5).
Table 1 shows that the average caffeine correction factor is .6 for clozapine. Assuming other variables are stable, including no changes in smoking patterns, if a patient whose clozapine dose is stabilized in a caffeine-free environment begins to regularly consume high quantities of caffeine, it may be safest to decrease the clozapine dose—for example, from 400 to 250 mg a day (400 mg a day x .6=240 mg a day). Only high quantities of caffeine seem to have significant clinical interactions with clozapine.

In the United States, brewed coffee is estimated to contain 85 mg of caffeine per 5 oz cup; instant coffee, 65 mg per 5 oz cup; decaffeinated coffee, 3 mg per 5 oz cup; tea, 40 mg per 5 oz cup; and caffeinated sodas, including caffeinated colas, 40 mg per 12 oz can. In Europe, brewed coffee is estimated to contain more caffeine (100 mg per 150 cc cup). Obviously, caffeinated over-the-counter medicines in pill form may have much more caffeine than caffeinated beverages (up to 200 mg per pill). No data are available that show what level of caffeine intake is safe for patients who are taking clozapine. Steady caffeine dosages for a patient who is stabilized and is taking clozapine should not be of concern for clinicians. However, it may be important to warn the patient to avoid "dramatic" changes—either up or down —in caffeine intake. However, no published data define "dramatic" change in caffeine intake.
Psychopharmacology: Atypical Antipsychotic Dosing: The Effect of Smoking and Caffeine

Роль L-метилфолата в терапии депрессивных расстройств

Folate is a water soluble B vitamin (B9), considered one of the 13 essential vitamins. The primary function of folate is the transfer of methyl and formyl groups, thus, it is essential for cell growth and reproduction, the breakdown and utilization of proteins, the formation of nucleic acids, red blood cell maturation, and a variety of CNS reactions. Dihydrofolate is the dietary form found in orange juice, spinach, asparagus, beans, liver, yeast, whole grain cereals, and eggs. Folic acid is the synthetic form of folate in over-the-counter vitamins and used to fortify the food supply (to help prevent neural tube defects, the FDA mandated folic acid fortification of flour in 1998). Folic acid is also the predominant form used in prescription strength prenatal vitamins. Both folic acid and dihydrofolate are not biologically active forms of folate, but are essentially pro-drugs, and must undergo enzymatic transformation to L-methylfolate in order to be used by cells, and unlike other forms of folate, L-methylfolate readily crosses the blood-brain barrier for use in the CNS.


Almost 85% of dietary folate and nearly all supplemental folic acid is absorbed into the venous system in the proximal small intestine. The enzymatic conversion begins in the intestinal wall—it is a three step process for dihydrofolate, and a four step process for folic acid (Slide 3). Folic acid is converted to dihydrofolate (DHF) by dihydrofolate reductase enzyme (DHFR), and DHF is then converted to tetrahydrofolate (THF). The conversion of THF to 5,10-methyleneTHF follows. Finally, the conversion of 5,10-methyleneTHF to L-methylfolate is achieved by the methyltetrahydrofolate reductase enzyme (MTHFR). This last step completes the four step transformation process by which the bioactive cofactor, L-methylfolate, is made available to the brain to be used in the synthesis of monoamine neurotransmitters associated with mood regulation (serotonin, norepinephrine, and dopamine).

There are five trials that examine folate therapy in depressive disorders. In a study59 with patients who had low or borderline low RBC folate, depressed patients on tricyclic antidepressants or MAOIs were augmented with methylfolate 15 mg (L-methylfolate 7.5 mg) experienced significantly greater clinical improvement and social improvement at 3 months (P<.02) and 6 months (P<.01) compared to patients treated with antidepressants alone. The methylfolate-augmented patients continued to improve for 6 months compared to patients augmented with placebo, and none experienced relapse. In a separate double-blind, controlled trial60 comparing methylfolate 50 mg/day to trazodone 100 mg/day, depressed patients experienced a significant decrease in HAM-D scores at 4 and 8 weeks in both groups, with response rates in the methylfolate group at 45%, and in the trazodone group (not statistically significant) at 29%.


An open label trial61 of methylfolate as monotherapy in elderly depressed subjects demonstrated an 81% response rate (>50% reduction in HAM-D) by 6 weeks of therapy. A second monotherapy study examined a depressed population of 36 chronic alcoholics. After a week of placebo wash-out, subjects received 4 weeks of 90 mg methylfolate therapy. This dosing (30 mg TID) significantly improved depressive symptoms based on the HAM-D scale with the majority reporting improved mood and less fatigue (P<.01).62 Alpert and colleagues63 conducted an open label trial augmenting selective serotonin reuptake inhibitor (SSRIs) with folinic acid in patients who had failed at least 4 weeks of SSRI therapy. The response to folinic acid was not robust (P<.01, n=22), but it was well tolerated overall.

The standard dose of L-methylfolate for the augmentation of antidepressants is one 7.5 mg tablet/day. No titration is necessary, and it is not associated with withdrawal symptoms at discontinuation. The maximum amount of L-methylfolate that can be absorbed in one dose is ~15 mg.67 If more than one 7.5 mg tablet/day is needed, it may be prudent to give in divided doses. All reported adverse events occur at placebo rates or lower, and overall it is an extremely well tolerated agent, allowing patients to continue L-methylfolate therapy as long as necessary to maintain remission. There are no known contraindications and no known drug interactions.

The Role of L-methylfolate in Depressive Disorders

Психотическая симптоматика после злоупотребления энергетическими напитками у больного шизофренией

Caffeine functions in the central nervous system as a competitive antagonist of adenosine receptors, A1 and A2A, and alters neurotransmitter release, including dopamine and glutamate. This dopamine release in the striatum may underlie caffeine's reinforcing properties, and the modulation of the mesolimbic dopamine pathway may be related to its psychotomimetic effect (1). Exaggerated effects may be seen in patients with schizophrenia using high-dose caffeine (2). The energy drink the patient in the present case consumed contained 160 mg of caffeine per can. The patient weighed 67 kg and therefore consumed approximately 20 mg/kg per day of caffeine. Psychosis has been reported at doses near 10 mg/kg per day (3), which is well below the known toxic dosage (150–200 mg/kg) but above the average intake by the numerous schizophrenia outpatients who use caffeine (1.8–4.1 mg/kg per day [depending on smoking status]) (4).

Psychosis Following Excessive Ingestion of Energy Drinks in a Patient With Schizophrenia

Кофеиновый психоз

[The patient reported drinking less than one case of beer annually. However, ~7 years before presentation, he had sharply increased his consumption of coffee from 10–12 cups/day to ~36 cups/day, a change in coffee consumption corroborated by his wife who made much of the coffee for him at home]

http://mbldownloads.com/0309CNS_Hedges.pdf