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Psychiatric Drugs and Antibiotics. When Two Worlds Collide

Alina Pleșea-Condratovici
Department of Morphological and Functional Sciences

Faculty of Medicine and Pharmacy
Dunărea de Jos University of Galați
Strada Domnească 47, Galați, Romania

Phone: 0336 130 108
aliaplesea@yahoo.com

Simona Lungu
Department of Clinical Medicine

Faculty of Medicine and Pharmacy
Dunărea de Jos University of Galați
Strada Domnească 47, Galați, Romania

Phone: 0336 130 108
drlungusimona@gmail.com

Mihai Mutică
Elisabeta Doamna Hospital of Psychiatry, Galați, Romania

mutica1@yahoo.com

Cătălin Pleșea-Condratovici
Department of Morphological and Functional Sciences

Faculty of Medicine and Pharmacy
Dunărea de Jos University of Galați
Strada Domnească 47, Galați, Romania

Phone: 0336 130 108
cmidr.pleseacatalin@gmail.com

Abstract
Background: Both psychotropic medication and antibiotic therapy are extensively

prescribed. In many cases, these medications are concurrent and the necessity to analyze this
particular drug interaction appears.

Aims: To identify in specialized medical databases what these interactions are, which is
their biochemical substrate, and which is the optimal method to avoid unwanted drug associations.

Method: Abstracts of PubMed database were automatically filtered using a specific search
tool, the keyword data being drug interactions psychotropics, antibiotics and their synonyms, and
websites dedicated to drug interactions were interrogated on the same subject.

Results and Discussion: Given that there is not enough clear data, especially for new
developed medicines, it seems that drug interactions between antibiotics and psychotropic drugs are
generally benign. Even if specialized web applications to identify drug interactions already exist,
their results often differ or are not consistent.

Conclusion: Although interactions between psychotropic and antibiotic drugs appear to be
generally benign, more valid data are needed to properly assess their impact on treatment efficiency
and the patient’s quality of life. Antibiotics must be prescribed when necessary and it is advisable to
avoid antibiotic classes with the most documented drug interactions: Fluoroquinolones, Macrolides
and Anti-tuberculosis drugs.

Keywords: Psychiatric Drugs; Antibiotics; Drug Interactions.

1. Introduction
There is a plethora of data in the literature that supports the idea of a pandemic of

psychiatric affections.

BRAIN – Broad Research in Artificial Intelligence and Neuroscience
Volume 10, Special Issue (June, 2019), ISSN 2067-3957

Results of the systematic review and meta-analysis indicated that approximately one in five
persons experienced a common mental disorder within a 12-month period across general population
surveys undertaken in 59 countries. The aggregate lifetime prevalence of common mental disorder
was estimated at 29.2% from 85 surveys undertaken across 39 countries (Steel et. al., 2014).

Accordingly, the consumption of psychotropic drugs is at a high level, 1 of 6 US adults
reported taking psychiatric drugs at least once (Moore & Mattison, 2017).

Antibiotics are the second most commonly prescribed class of medication in the United
States. An awareness and understanding of their potential effects on the central nervous system and
their interactions with psychotropic agents is important in the evaluation of neuropsychiatric signs
and symptoms in patients (Sternbach & State, 1997). Global antibiotic consumption had increased
by 65% from 2000 to 2015 (Klein et. al., 2018; Duceac et. al., 2018).

Because, on the one hand, psychiatric pathology is particularly frequent, often requiring
chronic medication, and, on the other hand, infectious pathology is also very common, antibiotics
being the second most prescribed medication, the situations in which the two therapeutic classes are
also very frequent.

In literature, an increasing prevalence of bacterial infections have been described for
patients with psychiatric disorders (Wang et. al., 2014).

Moreover, infections have been associated with increased risks for mental disorders, such as
schizophrenia and depression, and recent studies provide evidence for the involvement of infections
and the immune system in the etiology of a wide range of mental disorders in children and
adolescents (Köhler-Forsberg et. al., 2019; Trandafir et. al., 2018).

Classically, drug interaction refers to the concomitant administration of at least two drugs
resulting in different effects compared to the situation in which the drugs would be administered
individually (Ciubara et. al., 2018).

From the point of view of interaction mechanisms, we can differentiate pharmacokinetic
interactions, such as changes in absorption, distribution, metabolism and excretion, and
pharmacodynamic interactions, as with concomitant administration of agonist or antagonist
substances for the same receptor.

In medical practice three situations can arise in the drug interaction situation: potentiation of
effects (agonist, synergistic effect), reduction of effects (antagonistic effect) or appearance of new,
unwanted effects.

Knowing drug interactions is particularly important in practice. Synergistic effects can be
used to maximize the desired therapeutic effects, but caution should be taken to avoid overdosing.

Antagonist interaction should also be known to avoid combinations of drugs that decrease
each other's effects to a limit that makes them ineffective.

In the particular case of the interaction between psychotropic and antibiotics medications,
precautions should be taken to avoid situations where antibiotics become ineffective, not controlling
the infection, or where psychiatric medication leads to exacerbations of pathology or withdrawal
phenomena.

As a general rule, drug interactions should be avoided, or where this is difficult or
impossible, doses should be adjusted accordingly.

Most drug interactions take place at the metabolic stage, of particular importance being the
cytochrome P450. Almost all psychotropic drugs are metabolized at this level. Of the various
families that are present in human beings, the most interesting in this respect are the 1, 2 and 3, and
the most important enzymes are CYP1A2, CYP2C9, CYP2C19, CYP2D6, CYP2E1 and CYP3A4.
The majority of the enzymes are also involved in the metabolism of endogenous substances, such as
steroids or sex hormones, which is also important should there be interference with these
substances. As a result of these interactions, the function of the enzymes can either be stimulated
(enzyme induction) or inhibited (enzyme inhibition) (Normann et. al., 1998).

A. Pleșea-Condratovici, S. Lungu, M. Mutică, C. Pleșea-Condratovici - Psychiatric Drugs and Antibiotics. When Two
Worlds Collide

2. Methods
Information on “drug interactions” is spread over nearly 300,000 PubMed results. To select

relevant articles, a specific search tool was used, with keyword data being: drug interactions
psychotropics, antibiotics and their synonyms. The abstracts were manually screened for relevant
information and the results regarding psychotropic and antibiotics drugs interactions were
summarized in a table. Additionally, websites dedicated to drug interactions were interrogated on
the same subject and the results were compared with the previous findings and added to the table.

3. Results
Drug interactions between psychiatric medication and antibiotics appear to have only rare

significant clinical consequences, usually benign or under-investigated. There may be more subtle
interactions that seem to be underestimated or ignored.

The antibiotics classes most commonly involved in interactions with psychotropic
medication are Fluoroquinolones, Macrolides and Anti-tuberculosis drugs.

The most common interactions are those of the antagonist type in which the effect of both
classes of medication is reduced, and the the QT interval is prolonged. The most frequent
underlying mechanism seems to be the inhibition of cytochrome P450 enzymes.

Drug interactions are reported between antibiotics and typical and atypical antipsychotics,
antidepressants from all the classes, selective serotonin reuptake inhibitors, Monoamine oxidase
inhibitors, Tricyclics, and Serotonin norepinephrine reuptake inhibitors, Antianxiety/antipanic
medications, Stimulants, Mood stabilizers.

There are more adverse drug interactions reported for medicines that are used in practice for
a long time, and very few or none for new developed drugs. Even in cases where class membership,
structure, or mechanism of action justifies the suspicion of drug interactions, at least theoretically,
the data is inconsistent or lacking.

Because interactions are not always clinically evident, their effects are often attributed to
other causes and frequently clinicians fail to recognize and report them, so there is no clear
epidemiological data on their incidence.

There is a lot of inconsistent or contradictory data on drug interactions in both PubMed
literature and on web sites that provide information about drug interactions.

Table 1. Interactions between psychiatric drugs and antibiotics classes
Antibiotics

Psychotropics Pe

ni
ci

lli
ns

Ce
ph

al
os

po
ri

Fl
uo

ro
qu

in
ol

on
es

A
m

in
og

ly
co

si
de

M
on

ob
ac

ta
m

Ca
rb

ap
en

em
s

M
ac

ro
lid

G
ly

co
pe

pt
id

Su
lfo

na
m

id
es

Li
nc

om
yc

in
s

A
nt

it
ub

er
cu

lo
si

Te
tr

ac
yc

lin
es

Po
ly

pe
pt

id
es

O
th

A
nt

ip
sy

ch
ot

ic
s

Ty
pi

ca
l

Chlorpromazine 
Perphenazine 
Trifluoperazine q q
Mesoridazine
Fluphenazine q
Thiothixene
Molindone
Thioridazine q
Loxapine
Haloperidol 

A
t

yp
i

Aripiprazole 

BRAIN – Broad Research in Artificial Intelligence and Neuroscience
Volume 10, Special Issue (June, 2019), ISSN 2067-3957

Clozapine   
Ziprasidone  
Risperidone 
Quetiapine  
Olanzapine  

A
nt

id
ep

re
ss

an
ts

SS
R

Citalopram 
Escitalopram 
Fluvoxamine
Paroxetine
Fluoxetine
Sertraline q q 

M
A

O
Is

Selegiline
Isocarboxazid
Phenelzine
Tranylcypromine

TC
A

Clomipramine  q
Amoxapine 
Amitriptyline 
Desipramine
Nortriptyline  q
Doxepin  q
Trimipramine  q
Imipramine
Protiptyline

SN
RI

Desvenlafaxine
Venlafaxine q q
Duloxetine 

A
nt

ia
nx

y/
an

ti
pa

ni
c

m
ed

ic
at

io
ns

Lorazepam  
Buspirone
Propranolol
Clonazepam  
Chlordiazepoxide
Oxazepam  
Atenolol
Clorazepate
Diazepam  
Alprazolam  

St
im

u
la

nt
s:

(D)amphetamine  
Methylphenidate

M
oo

d
st

ab
ili Lamotrygine  

Lithium 

References given in parentheses: “Antianx” - Antianxiety/antipanic medications, “Sti” - Stimulants, “M” - Mood
stabilizers, “SSRIs” - Selective serotonin reuptake inhibitors, “MAOIs” - Monoamine oxidase inhibitors, “TCAs” -
Tricyclics, “SNRI” - Seretonin norepinephrine reuptake inhibitors, “q” - prolongation of the QT interval

4. Discussion
A significant number of new psychotropic drugs are introduced every year. Although not as

frequently, antibiotic classes and derivatives also appear. New drugs and drugs with a narrow
therapeutic area are most likely to cause serious negative drug interactions.

A. Pleșea-Condratovici, S. Lungu, M. Mutică, C. Pleșea-Condratovici - Psychiatric Drugs and Antibiotics. When Two
Worlds Collide

In the process of developing a new drug, it is impossible to study in vivo interactions with
all other drugs. Possible drug interactions can sometimes be estimated by looking at the theoretical
models of action of the drug at the carrier and the receptor levels, most frequently being analyzed at
the level of the cytochrome P450 enzyme assembly. This theoretical analysis is complicated by the
fact that in humans there are 5 isoenzymes involved in this process that can be modulated
differently from a large number of drugs and the clinical expression of these interactions is difficult
to predict (Straticiuc et. al., 2016).

A logical way to prevent potential drug interactions for a new drug would be to test
interactions at least for the most common association, which is also the case for antibiotics and
psychiatric drugs.

Another way in which drug interactions between anti-infectious therapy and psychotropic
medication are discovered is the publication of articles describing clinical cases of interactions.
These are usually case studies that describe well-documented clinical effects, for example lithium
intoxication reported in the case of a patient who was concomitantly treated with tetracycline. These
findings are strained by the fact that they are based on a small number of cases where the genotype,
phenotype, or other specific, individual factors can influence the outcome. Sometimes these results
are not reproducible to another patient or animal study.

Beyond the classic drug interactions, antibiotics and psychotropic drugs, psychiatric
pathology implicitly, seem to be linked by a particular mechanism. Recent studies identify links
between intestinal dysbiosis, commonly caused by broad spectrum antibiotics, and psychiatric
pathology, especially schizophrenia and depression. This phenomenon seems to be based on the
gut-brain axis biochemical signaling from the gastrointestinal tract to the central nervous system
(Zhu et. al., 2017; Ciubotaru et. al., 2016; “Drug Interactions Checker - For Drugs, Food &
Alcohol”, 2019; Drug Interaction Checker, 2019; Drug Interaction Checker | UCLA Health Library,
Los Angeles, CA, 2019).

Recognizing drug interactions based on memory is a burden for physicians. To summarize
treatments from diverse therapeutic areas is even more difficult for family doctors. The only viable
solution is to turn to specialized databases to identify drug interactions.

None of the web sites analyzed seems to offer the clinician the perfect solution to ensure the
absence of drug interactions. In some cases, the number of drug interactions is exaggerated,
probably by considering theoretical interaction mechanisms without quantifying the actual impact
on the effectiveness of therapy. In other cases, for interactions documented through clinical trials,
the response to the site query is null.

A desirable solution would be to implement, in the existing medical software used by
clinicians, a module that automatically provides 3-level warnings, caution, moderate or mildrisk on
possible drug interactions when writing an electronic prescription.

5. Conclusions
Although interactions between psychotropic and antibiotic drugs appear to be generally

benign, more valid data is needed to properly assess their impact on treatment efficiency and
patient’s quality of life.

Antibiotics must be prescribed for patients receiving concomitant psychiatric treatment only
when necessary.

When possible, it is advisable to avoid antibiotic classes with the most documented drug
interactions, such as Fluoroquinolones, Macrolides and Anti-tuberculosis drugs, and to analyze any
possible drug interaction using updated software applications.

When the association is absolutely necessary, the therapeutic response should be carefully
monitored, routine electrocardiographic testing for prolonged QT interval must be done and the
dosages should be adjusted accordingly.

BRAIN – Broad Research in Artificial Intelligence and Neuroscience
Volume 10, Special Issue (June, 2019), ISSN 2067-3957

Conflicts of Interest
The authors declare no conflict of interest.

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