Question: Does topamax cause mood depression?

Topiramate


Topiramate (brand name Topamax) is a broad-spectrum anticonvulsant (antiepilepsy) drug. In late 2012, topiramate was approved by the United States Food and Drug Administration (FDA) in combination with phentermine for weight loss. The drug had previously been used off-label for this purpose. Topiramate was originally produced by Ortho-McNeil Neurologics and Noramco, Inc., both divisions of the Johnson & Johnson Corporation. This medication was discovered in 1979 by Bruce E. Maryanoff and Joseph F. Gardocki during their research work at McNeil Pharmaceuticals.[1][2][3]
The commercial usage of Topiramate began in 1996.[4] Mylan Pharmaceuticals was granted final approval by the FDA for the sale of generic topiramate in the United States and the generic version was made available in September 2006.[5] The last patent for topiramate in the U.S. was for use in children and expired on February 28, 2009.[6]
Medical uses
Topiramate is used to treat epilepsy in children and adults, and it was originally used as an anticonvulsant.[7] In children, it is indicated for the treatment of Lennox-Gastaut syndrome, a disorder that causes seizures and developmental delay. It is most frequently prescribed for, the prevention of migraines.[7] It decreases the frequency of attacks.[8][9]
Pain
A 2018 review found topiramate of no use in chronic low back pain.[10] Topiramate has not been shown to work as a pain medicine in diabetic neuropathy, the only neuropathic condition in which it has been adequately tested.[11]
Other
Off label use for bipolar disorder treatment.[12][13][14] A more recent review, published in 2010, suggested a benefit of topiramate in the treatment of symptoms of borderline personality disorder, however the authors note that this was based only on one randomized controlled trial and requires replication.[15]
Topiramate has been used as a treatment for alcoholism.[16] The VA/DoD 2015 guideline on substance use disorders lists topiramate as a "strong for" in its recommendations for alcohol use disorder.[17]
Other uses include treatment of obesity[18][19] and antipsychotic-induced weight gain.[20][21] It is being studied to treat post traumatic stress disorder.[22]
Warnings and contraindications
People taking topiramate should be aware of the following risks: 
Avoid activities requiring mental alertness and coordination until drug effects are realized.
Topiramate may impair heat regulation,[23] especially in children. Use caution with activities leading to an increased core temperature, such as strenuous exercise, exposure to extreme heat, or dehydration.
Topiramate may cause visual field defects.[24]
Topiramate may decrease effectiveness of oestrogen-containing oral contraceptives.
Taking topiramate in the 1st trimester of pregnancy may increase risk of cleft lip/cleft palate in infant.[25]
As is the case for all antiepileptic drugs, it is advisable not to suddenly discontinue topiramate as there is a theoretical risk of rebound seizures.
Adverse effects
Adverse effects by incidence:[26][27][28][29]
Very common (>10% incidence) adverse effects include:

Dizziness
Weight loss
Paraesthesia - e.g., pins and needles
Somnolence
Nausea
Diarrhea
Fatigue
Nasopharyngitis
Depression

Uncommon (1-10% incidence) adverse effects include:

Weight gain
Anaemia
Disturbance in attention
Memory impairment
Amnesia
Cognitive disorder
Mental impairment
Psychomotor skills impaired
Convulsion
Coordination abnormal
Tremor
Lethargy
Hypoaesthesia (reduced sense of touch)
Nystagmus
Dysgeusia
Balance disorder
Dysarthria
Intention tremor
Sedation
Blurred vision
Diplopia (double vision)
Visual disturbance
Vertigo
Tinnitus
Ear pain
Dyspnoea
Epistaxis
Nasal congestion
Rhinorrhoea
Vomiting
Constipation
Abdominal pain upper
Dyspepsia
Abdominal pain
Dry mouth
Stomach discomfort
Paraesthesia oral
Gastritis
Abdominal discomfort
Nephrolithiasis
Pollakisuria
Dysuria
Alopecia (hair loss)
Rash
Pruritus
Arthralgia
Muscle spasms
Myalgia
Muscle twitching
Muscular weakness
Musculoskeletal chest pain
Anorexia
Decreased appetite
Pyrexia
Asthenia
Irritability
Gait disturbance
Feeling abnormal
Malaise
Hypersensitivity
Bradyphrenia (slowness of thought)
Insomnia
Expressive language disorder
Anxiety
Confusional state
Disorientation
Aggression
Mood altered
Agitation
Mood swings
Anger
Abnormal behaviour

Rarely, the inhibition of carbonic anhydrase may be strong enough to cause metabolic acidosis of clinical importance.[30]
The U.S. Food and Drug Administration (FDA) has notified prescribers that topiramate can cause acute myopia and secondary angle closure glaucoma in a small subset of people who take topiramate regularly.[31] The symptoms, which typically begin in the first month of use, include blurred vision and eye pain. Discontinuation of topiramate may halt the progression of the ocular damage and may reverse the visual impairment.
Preliminary data suggests that, as with several other anti-epileptic drugs, topiramate carries an increased risk of congenital malformations.[32] This might be particularly important for women who take topiramate to prevent migraine attacks. In March 2011, the FDA notified healthcare professionals and patients of an increased risk of development of cleft lip and/or cleft palate (oral clefts) in infants born to women treated with Topamax (topiramate) during pregnancy and placed it in Pregnancy Category D.[25]
Topiramate has been associated with a statistically significant increase in suicidality,[33] and "suicidal thoughts or actions" is now listed as one of the possible side effects of the drug "in a very small number of people, about 1 in 500."[23][34]
Overdose
Symptoms of acute and acute on chronic exposure to topiramate range from asymptomatic to status epilepticus, including in patients with no seizure history.[35][36] In children, overdose may also result in hallucinations.[36] Topiramate has been deemed the primary substance that led to fatal overdoses in cases that were complicated by polydrug exposure.[37] The most common signs of overdose are dilated pupils, somnolence, dizziness, psychomotor agitation, and abnormal, uncoordinated body movements.[35][36][37]
Symptoms of overdose may include but are not limited to:

Agitation
Depression
Speech problems
Blurred vision, double vision
Troubled thinking
Loss of coordination
Inability to respond to things around you
Loss of consciousness
Confusion and coma
Fainting
Upset stomach and stomach pain
Loss of appetite and vomiting
Shortness of breath; fast, shallow breathing
Pounding or irregular heartbeat
Muscle weakness
Bone pain
Seizures

A specific antidote is not available. Treatment is entirely supportive.
Interactions
Topiramate has many drug-drug interactions. Some of the most common are listed below:
As topiramate inhibits carbonic anhydrase, use with other inhibitors of carbonic anhydrase (e.g. acetazolamide) increases the risk of kidney stones.
Enzyme inducers (e.g. carbamazepine) can increase the elimination of topiramate, possibly necessitating dose escalations of topiramate.
Topiramate may increase the plasma-levels of phenytoin.
Topiramate itself is a weak inhibitor of CYP2C19 and induces CYP3A4; a decrease in plasma levels of estrogens and digoxin has been noted during topiramate therapy. This can reduce the effectiveness of oral contraceptives (birth control  pills); use of alternative birth control methods is recommended.[38] Neither intrauterine devices (IUDs) nor Depo-Provera are affected by topiramate.[38]
Alcohol may cause increased sedation or drowsiness, and increase the risk of having a seizure.
As listed in the 06/29/2005 label posted at the Drugs@FDA website page 14,'conditions or therapies that predispose to acidosis may be additive to the bicarbonate lowering effects of Topiramate'.[39]
Oligohidrosis and hyperthermia were reported in post-marketing reports about topiramate; antimuscarinic drugs (like trospium) can aggravate these disorders.
Pharmacology
Chemically, topiramate is a sulfamate modified fructose diacetonide - a rather unusual chemical structure for a pharmaceutical.
Topiramate is quickly absorbed after oral use. Most of the drug (70%) is excreted in the urine unchanged. The remainder is extensively metabolized by hydroxylation, hydrolysis, and glucuronidation. Six metabolites have been identified in humans, none of which constitutes more than 5% of an administered dose.
Several cellular targets have been proposed to be relevant to the therapeutic activity of topiramate.[40] These include (1) voltage-gated sodium channels; (2) high-voltage-activated calcium channels; (3) GABA-A receptors; (4) AMPA/kainate receptors; and (5) carbonic anhydrase isoenzymes. There is evidence that topiramate may alter the activity of its targets by modifying their phosphorylation state instead of by a direct action.[41] The effect on sodium channels could be of particular relevance for seizure protection. Although topiramate does inhibit high-voltage-activated calcium channels, the relevance to clinical activity is uncertain. Effects on specific GABA-A receptor isoforms could also contribute to the antiseizure activity of the drug. Topiramate selectively inhibits cytosolic (type II) and membrane associated (type IV) forms of carbonic anhydrase. The action on carbonic anhydrase isoenzymes may contribute to the drug’s side-effects, including its propensity to cause metabolic acidosis and calcium phosphate kidney stones.
Topiramate inhibits maximal electroshock and pentylenetetrazol-induced seizures as well as partial and secondarily generalized tonic-clonic seizures in the kindling model, findings predictive of a broad spectrum of activities clinically. Its action on mitochondrial permeability transition pores has been proposed as a mechanism.[42]
While many anticonvulsants have been associated with apoptosis in young animals, animal experiments have found that topiramate is one of the very few anticonvulsants [see: levetiracetam, carbamazepine, lamotrigine] that do not induce apoptosis in young animals at doses needed to produce an anticonvulsant effect.[43]
Detection in body fluids
Blood, serum, or plasma topiramate concentrations may be measured using immunoassay or chromatographic methods to monitor therapy, confirm a diagnosis of poisoning in hospitalized patients, or to assist in a medicolegal death investigation. Plasma levels are usually less than 10mg/L during therapeutic administration, but can range from 10–150mg/L in overdose victims.[44][45][46]












, Ben Green, Priory Lodge Education Ltd., 1997-99. Version 1.1
 in the PDB